Academic literature on the topic 'Molecular motors'
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Journal articles on the topic "Molecular motors"
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Kassem, Salma, Thomas van Leeuwen, Anouk S. Lubbe, Miriam R. Wilson, Ben L. Feringa, and David A. Leigh. "Artificial molecular motors." Chemical Society Reviews 46, no. 9 (2017): 2592–621. http://dx.doi.org/10.1039/c7cs00245a.
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Artificial molecular motors take inspiration from motor proteins, nature's solution for achieving directional molecular level motion. An overview is given of the principal designs of artificial molecular motors and their modes of operation. We identify some key challenges remaining in the field.
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KLUMPP, STEFAN, MELANIE J. I. MÜLLER, and REINHARD LIPOWSKY. "COOPERATIVE TRANSPORT BY SMALL TEAMS OF MOLECULAR MOTORS." Biophysical Reviews and Letters 01, no. 04 (2006): 353–61. http://dx.doi.org/10.1142/s1793048006000288.
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Molecular motors power directed transport of cargoes within cells. Even if a single motor is sufficient to transport a cargo, motors often cooperate in small teams. We discuss the cooperative cargo transport by several motors theoretically and explore some of its properties. In particular we emphasize how motor teams can drag cargoes through a viscous environment.
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NI, CHEN, and JUN-ZHONG WANG. "STM STUDIES ON MOLECULAR ROTORS AND MOTORS." Surface Review and Letters 25, Supp01 (2018): 1841004. http://dx.doi.org/10.1142/s0218625x18410044.
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Molecular motor is a nanoscale machine that consumes energy to produce work via the unidirectional and controlled movement. They are universal in nature and essential to numerous processes of life. When mounted onto solid surfaces, scanning tunneling microscopy (STM) is a powerful technique to characterize the molecular rotors and motors due to the atomic-scale resolution coupled with its ability to track the motion of molecular rotor and motor over time. Moreover, the molecular rotors and motors can be powered by STM tip through injecting tunneling electrons. This review addresses recent advances in the STM studies of the structure, motion, and manipulation of molecular rotors and motors. The developments of surface-mounted azimuthal and altitudinal rotor and motors, large-scale array of molecular rotors, as well as the molecular motors with translational motion will be addressed.
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Schliwa, Manfred, and Günther Woehlke. "Molecular motors." Nature 422, no. 6933 (2003): 759–65. http://dx.doi.org/10.1038/nature01601.
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Trybus, Kathleen M., and Vladimir I. Gelfand. "Molecular motors." Molecular Biology of the Cell 24, no. 6 (2013): 672. http://dx.doi.org/10.1091/mbc.e12-12-0873.
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Cross, R. A., and N. J. Carter. "Molecular motors." Current Biology 10, no. 5 (2000): R177—R179. http://dx.doi.org/10.1016/s0960-9822(00)00368-7.
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Berger, Florian, Corina Keller, Melanie J. I. Müller, Stefan Klumpp, and Reinhard Lipowsky. "Co-operative transport by molecular motors." Biochemical Society Transactions 39, no. 5 (2011): 1211–15. http://dx.doi.org/10.1042/bst0391211.
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Intracellular transport is often driven co-operatively by several molecular motors, which may belong to one or several motor species. Understanding how these motors interact and what co-ordinates and regulates their movements is a central problem in studies of intracellular transport. A general theoretical framework for the analysis of such transport processes is described, which enables us to explain the behaviour of intracellular cargos by the transport properties of individual motors and their interactions. We review recent advances in the theoretical description of motor co-operativity and discuss related experimental results.
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Spector, Alexander A. "Effectiveness, Active Energy Produced by Molecular Motors, and Nonlinear Capacitance of the Cochlear Outer Hair Cell." Journal of Biomechanical Engineering 127, no. 3 (2005): 391–99. http://dx.doi.org/10.1115/1.1894233.
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Cochlear outer hair cells are crucial for active hearing. These cells have a unique form of motility, named electromotility, whose main features are the cell’s length changes, active force production, and nonlinear capacitance. The molecular motor, prestin, that drives outer hair cell electromotility has recently been identified. We reveal relationships between the active energy produced by the outer hair cell molecular motors, motor effectiveness, and the capacitive properties of the cell membrane. We quantitatively characterize these relationships by introducing three characteristics: effective capacitance, zero-strain capacitance, and zero-resultant capacitance. We show that zero-strain capacitance is smaller than zero-resultant capacitance, and that the effective capacitance is between the two. It was also found that the differences between the introduced capacitive characteristics can be expressed in terms of the active energy produced by the cell’s molecular motors. The effectiveness of the cell and its molecular motors is introduced as the ratio of the motors’ active energy to the energy of the externally applied electric field. It is shown that the effectiveness is proportional to the difference between zero-strain and zero-resultant capacitance. We analyze the cell and motor’s effectiveness within a broad range of cellular parameters and estimate it to be within a range of 12%–30%.
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Endow, S. A. "Molecular motors--a paradigm for mutant analysis." Journal of Cell Science 113, no. 8 (2000): 1311–18. http://dx.doi.org/10.1242/jcs.113.8.1311.
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Molecular motors perform essential functions in the cell and have the potential to provide insights into the basis of many important processes. A unique property of molecular motors is their ability to convert energy from ATP hydrolysis into work, enabling the motors to bind to and move along cytoskeletal filaments. The mechanism of energy conversion by molecular motors is not yet understood and may lead to the discovery of new biophysical principles. Mutant analysis could provide valuable information, but it is not obvious how to obtain mutants that are informative for study. The analysis presented here points out several strategies for obtaining mutants by selection from molecular or genetic screens, or by rational design. Mutants that are expected to provide important information about the motor mechanism include ATPase mutants, which interfere with the nucleotide hydrolysis cycle, and uncoupling mutants, which unlink basic motor activities and reveal their interdependence. Natural variants can also be exploited to provide unexpected information about motor function. This general approach to uncovering protein function by analysis of informative mutants is applicable not only to molecular motors, but to other proteins of interest.
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Pooler, Daisy R. S., Anouk S. Lubbe, Stefano Crespi, and Ben L. Feringa. "Designing light-driven rotary molecular motors." Chemical Science 12, no. 45 (2021): 14964–86. http://dx.doi.org/10.1039/d1sc04781g.
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Various families of light-driven rotary molecular motors and the key aspects of motor design are discussed. Comparisons are made between the strengths and weaknesses of each motor. Challenges, applications, and future prospects are explored.
Dissertations / Theses on the topic "Molecular motors"
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Neetz, Manuel. "Collective behavior of molecular motors." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-85935.
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Microtubule associated molecular motors are involved in a multitude of fundamental cellular processes such as intracellular transport and spindle positioning. During these movements multiple motor proteins often work together and are, therefore, able to exert high forces. Thus force generation and sensing are common mechanisms for controlling motor driven movement. These mechanisms play a pivotal role when motor proteins antagonize each other, e.g. to facilitate oscillations of the spindle or the nucleus.
Single motor proteins have been characterized in depth over the last two decades, our understanding of the collective behavior of molecular motors remains, however, poor. Since motor proteins often cooperate while they walk along microtubules, it is necessary to describe their collective reaction to a load quantitatively in order to understand the mechanism of many motor-driven processes.
I studied the antagonistic action of many molecular motors (of one kind) in a gliding geometry. For this purpose I crosslinked two microtubules in an antiparallel fashion, so that they formed \"doublets\". Then I observed the gliding motility of these antiparallel doublets and analyzed the gliding velocity with respect to the relative number of motors pulling or pushing against each other. I observed that the antiparallel doublets gliding on conventional kinesin-1 (from Drosophila melanogaster) as well as cytoplasmic dynein (from Saccharomyces cerevisae) exhibited two distinct modes of movement, slow and fast, which were well separated. Furthermore I found a bistability, meaning, that both kinds of movement, slow and fast, occurred at the same ratio of antagonizing motors. Antiparallel doublets gliding on the non-processive motor protein Ncd (the kinesin-14 from D. melanogaster) showed, however, no bistability. The collective dynamics of all three motor proteins were described with a quantitative theory based on single-motor properties.
Furthermore the response of multiple dynein motors towards an external, well-defined load was measured in a gliding geometry by magnetic tweezing. Examples of multi-motor force-velocity relationships are presented and discussed. I established, furthermore, a method for counting single surface immobilized motors to guide the evaluation of the tweezing experiments.
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Vilfan, Andrej. "Collective dynamics of molecular motors." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=959980024.
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Jaster, Nicole. "Ratchet models of molecular motors." Phd thesis, Universität Potsdam, 2003. http://opus.kobv.de/ubp/volltexte/2005/90/.
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Transportvorgänge in und von Zellen sind von herausragender Bedeutung für das Überleben des Organismus. Muskeln müssen sich kontrahieren können, Chromosomen während der Mitose an entgegengesetzte Enden der Zelle bewegt und Organellen, das sind von Membranen umschlossene Kompartimente, entlang molekularer Schienen transportiert werden. <br />
Molekulare Motoren sind Proteine, deren Hauptaufgabe es ist, andere Moleküle zu bewegen. Dazu wandeln sie die bei der ATP-Hydrolyse freiwerdende chemische Energie in mechanische Arbeit um. Die Motoren des Zellskeletts gehören zu den drei Superfamilien Myosin, Kinesin und Dynein. Ihre Schienen sind Filamente des Zellskeletts, Actin und die Microtubuli. <br />
In dieser Arbeit werden stochastische Modelle untersucht, welche dazu dienen, die Fortbewegung dieser linearen molekularen Motoren zu beschreiben. Die Skala, auf der wir die Bewegung betrachten, reicht von einzelnen Schritten eines Motorproteins bis in den Bereich der gerichteten Bewegung entlang eines Filaments. Ein Einzelschritt überbrückt je nach Protein etwa 10 nm und wird in ungefähr 10 ms zurückgelegt. Unsere Modelle umfassen M Zustände oder Konformationen, die der Motor annehmen kann, während er sich entlang einer eindimensionalen Schiene bewegt. An K Orten dieser Schiene sind Übergänge zwischen den Zuständen möglich. Die Geschwindigkeit des Proteins lässt sich in Abhängigkeit von den vertikalen Übergangsraten zwischen den einzelnen Zuständen analytisch bestimmen. Wir berechnen diese Geschwindigkeit für Systeme mit bis zu vier Zuständen und Orten und können weiterhin eine Reihe von Regeln ableiten, die uns einschätzen helfen, wie sich ein beliebiges vorgegebenes System verhalten wird. <br />
Darüber hinaus betrachten wir entkoppelte Subsysteme, also einen oder mehrere Zustände, die keine Verbindung zum übrigen System haben. Mit einer bestimmten Wahrscheinlichkeit kann ein Motor einen Zyklus von Konformationen durchlaufen, mit einer anderen Wahrscheinlichkeit einen davon unabhängigen anderen. <br />
Aktive Elemente werden in realen Transportvorgängen durch Motorproteine nicht auf die Übergänge zwischen den Zuständen beschränkt sein. In verzerrten Netzwerken oder ausgehend von der diskreten Mastergleichung des Systems können auch horizontale Raten spezifiziert werden und müssen weiterhin nicht mehr die Bedingungen der detaillierten Balance erfüllen. Damit ergeben sich eindeutige, komplette Pfade durch das jeweilige Netzwerk und Regeln für die Abhängigkeit des Gesamtstroms von allen Raten des Systems. Außerdem betrachten wir die zeitliche Entwicklung für vorgegebene Anfangsverteilungen. <br />
Bei Enzymreaktionen gibt es die Idee des Hauptpfades, dem diese bevorzugt folgen. Wir bestimmen optimale Pfade und den maximalen Fluss durch vorgegebene Netzwerke. <br />
Um darüber hinaus die Geschwindigkeit des Motors in Abhängigkeit von seinem Treibstoff ATP angeben zu können, betrachten wir mögliche Reaktionskinetiken, die den Zusammenhang zwischen den unbalancierten Übergangsraten und der ATP-Konzentration bestimmen. Je nach Typ der Reaktionskinetik und Anzahl unbalancierter Raten ergeben sich qualitativ unterschiedliche Verläufe der Geschwindigkeitskurven in Abhängigkeit von der ATP-Konzentration. <br />
Die molekularen Wechselwirkungspotentiale, die der Motor entlang seiner Schiene erfährt, sind unbekannt.Wir vergleichen unterschiedliche einfache Potentiale und die Auswirkungen auf die Transportkoeffizienten, die sich durch die Lokalisation der vertikalen Übergänge im Netzwerkmodell im Vergleich zu anderen Ansätzen ergeben.<br>Transport processes in and of cells are of major importance for the survival of the organism. Muscles have to be able to contract, chromosomes have to be moved to opposing ends of the cell during mitosis, and organelles, which are compartments enclosed by membranes, have to be transported along molecular tracks.<br />
Molecular motors are proteins whose main task is moving other molecules.For that purpose they transform the chemical energy released in the hydrolysis of ATP into mechanical work. The motors of the cytoskeleton belong to the three super families myosin, kinesin and dynein. Their tracks are filaments of the cytoskeleton, namely actin and the microtubuli. <br />
Here, we examine stochastic models which are used for describing the movements of these linear molecular motors. The scale of the movements comprises the regime of single steps of a motor protein up to the directed walk along a filament. A single step bridges around 10 nm, depending on the protein, and takes about 10 ms, if there is enough ATP available. Our models comprise M states or conformations the motor can attain during its movement along a one-dimensional track. At K locations along the track transitions between the states are possible. The velocity of the protein depending on the transition rates between the single states can be determined analytically. We calculate this velocity for systems of up to four states and locations and are able to derive a number of rules which are helpful in estimating the behaviour of an arbitrary given system.<br />
Beyond that we have a look at decoupled subsystems, i.e., one or a couple of states which have no connection to the remaining system. With a certain probability a motor undergoes a cycle of conformational changes, with another probability an independent other cycle. <br />
Active elements in real transport processes by molecular motors will not be limited to the transitions between the states. In distorted networks or starting from the discrete Master equation of the system, it is possible to specify horizontal rates, too, which furthermore no longer have to fulfill the conditions of detailed balance. Doing so, we obtain unique, complete paths through the respective network and rules for the dependence of the total current on all the rates of the system. Besides, we view the time evolutions for given initial distributions. <br />
In enzymatic reactions there is the idea of a main pathway these reactions follow preferably. We determine optimal paths and the maximal flow for given networks. <br />
In order to specify the dependence of the motor's velocity on its fuel ATP, we have a look at possible reaction kinetics determining the connection between unbalanced transitions rates and ATP-concentration. Depending on the type of reaction kinetics and the number of unbalanced rates, we obtain qualitatively different curves connecting the velocity to the ATP-concentration. <br />
The molecular interaction potentials the motor experiences on its way along its track are unknown. We compare different simple potentials and the effects the localization of the vertical rates in the network model has on the transport coefficients in comparison to other models.
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Müller, Melanie J. I. "Bidirectional transport by molecular motors." Phd thesis, Universität Potsdam, 2008. http://opus.kobv.de/ubp/volltexte/2008/1871/.
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In biological cells, the long-range intracellular traffic is powered by molecular motors which transport various cargos along microtubule filaments. The microtubules possess an intrinsic direction, having a 'plus' and a 'minus' end. Some molecular motors such as cytoplasmic dynein walk to the minus end, while others such as conventional kinesin walk to the plus end. Cells typically have an isopolar microtubule network. This is most pronounced in neuronal axons or fungal hyphae. In these long and thin tubular protrusions, the microtubules are arranged parallel to the tube axis with the minus ends pointing to the cell body and the plus ends pointing to the tip.
In such a tubular compartment, transport by only one motor type leads to 'motor traffic jams'. Kinesin-driven cargos accumulate at the tip, while dynein-driven cargos accumulate near the cell body. We identify the relevant length scales and characterize the jamming behaviour in these tube geometries by using both Monte Carlo simulations and analytical calculations.
A possible solution to this jamming problem is to transport cargos with a team of plus and a team of minus motors simultaneously, so that they can travel bidirectionally, as observed in cells. The presumably simplest mechanism for such bidirectional transport is provided by a 'tug-of-war' between the two motor teams which is governed by mechanical motor interactions only. We develop a stochastic tug-of-war model and study it with numerical and analytical calculations. We find a surprisingly complex cooperative motility behaviour. We compare our results to the available experimental data, which we reproduce qualitatively and quantitatively.<br>In biologischen Zellen transportieren molekulare Motoren verschiedenste Frachtteilchen entlang von Mikrotubuli-Filamenten. Die Mikrotubuli-Filamente besitzen eine intrinsische Richtung: sie haben ein "Plus-" und ein "Minus-"Ende. Einige molekulare Motoren wie Dynein laufen zum Minus-Ende, während andere wie Kinesin zum Plus-Ende laufen. Zellen haben typischerweise ein isopolares Mikrotubuli-Netzwerk. Dies ist besonders ausgeprägt in neuronalen Axonen oder Pilz-Hyphen. In diesen langen röhrenförmigen Ausstülpungen liegen die Mikrotubuli parallel zur Achse mit dem Minus-Ende zum Zellkörper und dem Plus-Ende zur Zellspitze gerichtet.
In einer solchen Röhre führt Transport durch nur einen Motor-Typ zu "Motor-Staus". Kinesin-getriebene Frachten akkumulieren an der Spitze, während Dynein-getriebene Frachten am Zellkörper akkumulieren. Wir identifizieren die relevanten Längenskalen und charakterisieren das Stauverhalten in diesen Röhrengeometrien mit Hilfe von Monte-Carlo-Simulationen und analytischen Rechnungen.
Eine mögliche Lösung für das Stauproblem ist der Transport mit einem Team von Plus- und einem Team von Minus-Motoren gleichzeitig, so dass die Fracht sich in beide Richtungen bewegen kann. Dies wird in Zellen tatsächlich beobachtet. Der einfachste Mechanismus für solchen bidirektionalen Transport ist ein "Tauziehen" zwischen den beiden Motor-Teams, das nur mit mechanischer Interaktion funktioniert. Wir entwickeln ein stochastisches Tauzieh-Modell, das wir mit numerischen und analytischen Rechnungen untersuchen. Es ergibt sich ein erstaunlich komplexes Motilitätsverhalten. Wir vergleichen unsere Resultate mit den vorhandenen experimentellen Daten, die wir qualitativ und quantitativ reproduzieren.
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Qi, Fei. "Light-driven molecular rotary motors." HKBU Institutional Repository, 2017. https://repository.hkbu.edu.hk/etd_oa/434.
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In the past two decades, a number of artificial molecular motors have been constructed using organic molecules as components which can perform unidirectional motion. Among the best-known examples are the light-activated molecular rotary motors synthesized and analyzed in B. L. Feringa's lab. Yet there is limited understanding of the photoisomerization and thermal isomerization processes that control the speed and energy conversion efficiency of these molecular devices. The present thesis work aims at: 1) developing a computational methodology to provide the atomic and electronic details that allow for quantitative descriptions of light-activated molecular motion, 2) improving the understanding of the physical principles governing photo- and thermal-isomerization processes in specific molecular systems, and 3) proposing a new strategy of molecule design to assist experimental investigations. A key component in our methodology is the calculation of the potential energy surface (PES) spanned by collective atomic coordinates using ab initio quantum mechanical methods. This is done both for the electronic ground state, which is relatively straightforward, and for the photo-excited state, which is more involved. Once the PES is known, classical statistical mechanical methods can be used to analyze the dynamics of the slow variables from which information about the rotational motion can be extracted. Calculation of the PES is computationally expensive if one were to sample the very high dimensional space of the atomic coordinates. A new method, based on the torque experienced by individual atoms, is developed to capture key aspects of the intramolecular relaxation in terms of angular variables associated with the rotational degrees of freedom. The effectiveness of the approach is tested on specific light-driven molecular rotary motors that were successfully synthesized and analyzed in previous experiments. Finally, based on the experience accumulated in this study, a new molecular rotary motor driven by visible light is proposed to reach MHz rotational frequency.
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Keller, Peter. "Mathematical modeling of molecular motors." Universität Potsdam, 2013. http://opus.kobv.de/ubp/volltexte/2013/6304/.
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Amongst the many complex processes taking place in living cells, transport of cargoes across the cytosceleton is fundamental to cell viability and activity. To move cargoes between the different cell parts, cells employ Molecular Motors. The motors operate by transporting cargoes along the so-called cellular micro-tubules, namely rope-like structures that connect, for instance,
the cell-nucleus and outer membrane. We introduce a new Markov Chain, the killed Quasi-Random-Walk, for such transport molecules and derive properties like the maximal run length and time. Furthermore we introduce permuted balance, which is a more flexible extension of the ordinary reversibility and introduce the notion of Time Duality, which compares certain passage times pathwise. We give a number of sufficient conditions for Time Duality based on the geometry of the transition graph. Both notions are closely related to properties of the killed Quasi-Random-Walk.
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Pérez, Carrasco Rubén. "Mechano–chemical study of rotatory molecular motors." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/108039.
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Cells are the minimum unit of life. They are born, they eat, the may grow, they may move, and, eventually, they die. By contrast, from a physicist point of view, cells are systems out of equilibrium continuously transducing between matter, energy and information. This transduction is what grants the cell their active properties. In order to perform such tasks, cells have a set of macromolecules, a machinery, which are called, Molecular Motors or Molecular Machines. The operation of molecular motors is multiple. For instance, kinesins are molecular motors able to transport cargoes along the cell, or the Bacterial Flagellar Motor works as a nanometric ionic turbine transmitting its rotation to bacterial flagella propelling the cell.
The energy input of such nanometric devices have two primary sources. On one hand the hydrolysis of nucleotide derivatives, such as ATP. On the other hand, molecular motors can also be found in biological membranes obtaining energy from the natural flux of ions crossing the membrane due to mechano-chemical energetic differences at each side.
The recycling of ATP molecules takes place in another molecular machine, the F0F1 ATP synthase. F0F1 is made up of two subunits that can be separated themselves in two different molecular machines. This way, the F1 motor can couple a rotatory motor with the synthesis/hydrolysis of ATP.
Understanding the working of molecular motors is not straightforward. The transduction processes result from a complex set of interactions of all the molecules conforming the motor plus all the interactions with the surrounding molecules. Thus, different approaches with different levels of abstraction are necessary. In the current thesis, molecular motors are studied through the identification of the energetic transduction cycles out of the trajectory of the motor. Trajectories allow to identify the different mechanical and chemical processes driving the motor and allow to propose a spatio-temporal potential for the motor that give information of the energetic performance of the motor such as power and efficiency.
This analysis is performed on the F1 motor (in its hydrolysis regime). Such analysis allowed to identify the origin of two well differentiated mechanical and chemical processes that were quantified by means of the reaction kinetics theory and the overdamped dynamics associated with the nanometric biological scale. From this analysis resulted a prediction for the average velocity of the motor with the experimental control parameters. The resulting velocity matches experimental measures of the average velocity without fitting any parameter since all the parameters needed can be extracted from alternative experimental assays.
The appealing results of the average velocity lead to a proposal of motor potential for the F1 motor consisting on two linear piece-wise potentials flashing between them. Each potential presenting the experimental characteristics observed when the catalytic site of the motor is empty or occupied. The potential also hold the substepping mechanism observed experimentally. Thus, the resulting potential can be tested, together with the overdamped dynamics of the potential and the thermal fluctuations characteristic of the biological cellular scale. This results in a Langevin equation leading the dynamics of the motor. Again, the stochastic dynamics proposed are able to reproduce the velocity of the motor returning a better approximation than the deterministic approach. As happened in the previous case, there is no fitting in the parameters to test the validity of the velocity expression. Actually, the model is able to predict the measured substep angle from optimisation arguments. The mismatch between the deterministic and the stochastic results was identified as a result of a loss of ATP hydrolysis events due to thermal fluctuations that has been also properly quantified through the Fokker-Planck formalism of the corresponding Langevin equation.
The motor potential proposed was also used to study experimental assays of the F1 motor working against conservative forces. The effect of a conservative torque in the working of the motor contains contributions both mechanical and chemical. Altogether, this contributions were successfully addressed presenting again an analytical and stochastic prediction for the velocity of the motor that matches the experimental observations without the need of any parameter fitting. This analysis also entailed a study of the energetic performance of the motor which is unavailable experimentally. The results show a complete divergence between the stochastic and deterministic predictions. The divergence is specially dramatical near the stall force of the motor where the determenistic analysis predicts an efficiency maximum and the stochastic analysis returns a null efficiency. This points out that the stochastic effects are very relevant to the energetic performance of the motor and can not be missed in a proper energetic study of a molecular machine.
Besides the study of the F1 motor, also a rotatory device working with an ionic flux was analised. The aim of the analysis was the devise of a minimal mechanistic turbine and the study of its main working features. Such a machine is composed by a mobile piston with periodic boundary conditions at both ends of a nanometric channel separating two particle reservoirs. Hence, the turbine is able to transduce energy between the flux of ions and an external force hindering the natural motion of the piston. Again, thermal fluctuations provide a stochastic dynamic that must be studied through a Langevin equation that can be tackled analytically. This study revealed that the velocity and the flux are not coupled. Specially, two different stall forces appear for the motor. One for the velocity and one for the flux. This results in an intermediate zone where there is a continuous leakage of ions that does not allow any energetic output. This effect is originated from thermal fluctuations. Thus, when the energetic performance is evaluated, a similar behaviour than the one obtained for the F1 motor is recuperated. This minimal model was extended with more complex turbines that take into account more thoroughly the biophysics of molecular machines. All of them result in the same energetic landscape where a minimum of efficiency is obtained near the stall of the motor.
Additionally, a new formalism has been developed to simplify the resulting Langevin equations (Fokker-planck white noise limit) and a new algorithm has been devised able to integrate Langevin equations with non-continuous multiplicative noise<br>Los Motores Moleculares son macromoléculas biológicas que se encargan de hacer las transducciones energéticas necesarias dentro de las células. Este trabajo estudia la transformación de energía de motores moleculares rotatorios reales principalmente la F1-ATPasa, el Motor Flagelar de las Bacterias y el F0.
Para estudiar la dinámica del motor se han utilizado ecuaciones de Langevin sobreamortiguadas que recogen la importancia de las fluctuaciones térmicas, así como las fuerzas externas aplicadas al motor (conservativas y disipativas) y el potencial interno del motor que contiene la información físico-química de su comportamiento.
Este estudio se ha aplicado a la F1-ATPasa, que se puede estudiar tanto analíticamente, obviando las fluctuaciones térmicas como desde su naturaleza estocástica mediante potenciales intermitentes. En ambos casos, el modelo es capaz de describir la dinámica del motor y su dependencia con los diferentes parámetros controlables experimentalmente: Concentración de ATP, fuerza disipativa y fuerza conservativa.
En el mismo sentido se ha diseñado una turbina nanoscópica que recoge los principios básicos de la interacción mecánica entre un flujo de iones y la rotación del motor. En ambos casos, tanto en la turbina como en el F1 se observa que el ruido térmico no afecta mucho a la velocidad del motor y en cambio produce cambios enormes en parámetros energéticos como la potencia o la eficiencia. Concretamente, el escenario clásico en que un máximo de eficiencia se obtiene para la fuerza de calado desaparece obteniendo nuevos regímenes óptimos de trabajo.
Adicionalmente, se ha desarrollado un formalismo para simplificar las ecuaciones de Langevin obtenidas (límite de ruido blanco) y se ha diseñado un nuevo algoritmo para integrar ecuaciones de Langevin en las cuales el ruido multiplicativo es discontinuo en el espacio.
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Li, Quan. "Integrated motions of light driven molecular motors at macroscopic scale." Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAF001/document.
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Dans la nature, des moteurs moléculaires tells que l'ATP synthase ou la kinésine peuvent consommer de l'énergie pour générer du mouvement et ainsi assurer des fonctions essentielles comme le transport ou la synthèse de molécules. La préparation de moteurs artificiels capables de fournir un travail à différentes échelles est un défi important pour les chimistes. Dans ce travail, nous avons conçu et synthétisé de manière stéréosélective un moteur moléculaire unidirectionnel et hautement fonctionnalisé à l'échelle du gramme. La fonctionnalisation orthogonale du moteur permet de l'intégrer dans des matériaux polymères. Grâce à une réaction de "click" réalisée sous différentes conditions de dilution, nous avons pu obtenir soit une macromolécule bicyclique en forme de 8 soit un gel de polymers dont les moteurs constituent les points de réticulation. Sous irradiation UV, les moteurs tournent ce qui enroule les chaines de polymers. Pour le bicycle, la taille caractéristique de la macromolécule diminue tandis que la morphologie évolue vers une pelote étirée. Dans le cas du gel, suite à la rotation des moteurs, l'enroulement des chaines conduit à une contraction du gel de l'ordre de 80% en volume. C'est le premier exemple d'intégration de mouvements moléculaires hors équilibre résultant en une réponse observable à l'échelle macroscopique. Ce travail ouvre des perspectives intéressantes dans le domaine des nanotechnologies ainsi que dans celui de l'énergie<br>Natural molecular motors such as ATP synthase, myosin, kinesin and dynein can convert conformationalchanges, due to chemical energy input, into directed motion for catalysis and transport. Preparing artificial molecular motors and making them work at different scales (from nano to macroscopic scale) have been long-term challenges. Herein we designed and synthesized a light driven rotary molecular motor in highly enantiopure form and in gram scale. This motor is featured by two orthogonal functionalities on its upper and lower part, allowing its further integration into polymeric materials. By performing click reaction under different concentration conditions, either an eight shaped motor-polymer conjugate or a gel containing motors as reticulation units could be obtained. Upon UV irradiation, the polymer chains could be entangled due to the rotation of this motor. For eight shaped polymer, the dimension was changed towards smaller dimension, and the morphology was changed from cycle to collapsed coils (spherical or more elongated). For the gel, due to the twisting of polymer chains induced by the rotation of the motor, it could be contracted significantly (80 %) compared with its original volume. The integration of machines which display motions out of equilibrium at nanoscale to movement in the macroscopic world which is extensively used in natural systems will open very interesting prospects in nanotechnology for further developments
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Simoes, Fabio Andre Amaral Lopes. "Cytoskeleton and molecular motors in the causation of motor neuron diseases." Thesis, University of Brighton, 2018. https://research.brighton.ac.uk/en/studentTheses/2629bd8d-bbba-4360-9ba2-d77733e431ad.
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Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy with lower extremity predominance (SMA-LED) are motor neuron diseases defined by the loss of motor neurons. RNA metabolism and molecular transport have both become increasingly implicated in the pathogenesis of motor neuron diseases. As such, this thesis explores the role of TAR-DNA binding protein 43 (TDP-43) in the regulation of peripherin expression in ALS, and the molecular consequences of mutations in DYNC1H1, a component of the cytoplasmic dynein motor complex, in SMA-LED. TDP-43 is a DNA/RNA binding protein implicated in ALS pathogenesis. Recent evidence suggests that TDP-43 regulates peripherin, an ALS associated intermediate filament protein. Here, analysis of peripherin in the lumbar spinal cord of TDP-43<sup>+/F210I</sup> mice revealed a significant increase in the levels of Per-45, a shift towards an increase in Per-58 in the Triton X-100 soluble fraction that did not reach statistical significance, and an increase in an isoform of 50 kDa in the insoluble fraction. These changes in the expression of peripherin in TDP-43<sup>+/F210I</sup> mice may indicate a regulatory role for TDP-43 in peripherin expression, which could contribute to ALS pathology. Furthermore, there is evidence that defects in neurodevelopment are present in SMA-LED. Analysis of paxillin, a key focal adhesion protein in mouse embryonic fibroblasts from the Legs at odd angles (Loa) model of SMA-LED was performed, which indicated a reduction in its expression which may underpin the previously reported migration phenotypes in these cells. This data provides further evidence that SMA-LED may be a neurodevelopmental disorder. Furthermore, analysis revealed that the Golgi apparatus in DYNC1H1<sup>+/D338N</sup> patient fibroblasts was significantly condensed, while in BICD2<sup>+/I189F</sup> fibroblasts there was a decrease in localisation of dynein to the Golgi. The lack of dynein at the Golgi in BICD2<sup>+/I189F</sup> fibroblasts indicates that BICD2 may be necessary for the recruitment of the molecular motor to the organelle. These Golgi phenotypes may also contribute to impaired migration in disease. Importantly, analysis of DYNC1H1<sup>+/D338N</sup> patient fibroblasts and mouse embryonic fibroblasts (MEFs) from the Loa mouse strain showed a significant decrease in α-tubulin acetylation, a phenotype previously seen in another DYNC1H1 substitution. In conclusion, these data support previous data which suggested that peripherin expression is altered in the context of TDP-43 mutations, potentially contributing to ALS pathology. Additionally, Golgi phenotypes were found in both DYNC1H1<sup>+/D338N</sup> and BICD2<sup>+/I189F</sup> fibroblasts with potential consequences for cellular migration. Finally, decreased microtubule acetylation may be a common factor in SMA-LED linked with DYNC1H1 mutations. The conserved nature of this phenotype could indicate a potential target for therapeutics.
Books on the topic "Molecular motors"
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Ann, Sperry O. Molecular Motors. Humana Press, 2007. http://dx.doi.org/10.1385/1597454907.
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Sperry, Ann O., ed. Molecular Motors. Humana Press, 2007. http://dx.doi.org/10.1007/978-1-59745-490-2.
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Lavelle, Christophe, ed. Molecular Motors. Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8556-2.
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George, Banting, Higgins S. J, and Biochemical Society (Great Britain), eds. Molecular motors. Portland Press, 2000.
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Lavelle, Christophe, and Antoine Le Gall, eds. Molecular Motors. Springer US, 2025. https://doi.org/10.1007/978-1-0716-4280-1.
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Jean-Pierre, Sauvage, and Amendola V, eds. Molecular machines and motors. Springer, 2001.
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Credi, Alberto, Serena Silvi, and Margherita Venturi, eds. Molecular Machines and Motors. Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-08678-1.
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Sauvage, Jean-Pierre, V. Amendola, R. Ballardini, et al., eds. Molecular Machines and Motors. Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/3-540-44421-1.
Full textBook chapters on the topic "Molecular motors"
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Cerofolini, Gianfranco. "Molecular Motors." In Nanoscale Devices. Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-92732-7_11.
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Bressloff, Paul C. "Molecular motors." In Interdisciplinary Applied Mathematics. Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-72515-0_4.
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Klumpp, Stefan, Corina Keller, Florian Berger, and Reinhard Lipowsky. "Molecular Motors: Cooperative Phenomena of Multiple Molecular Motors." In Multiscale Modeling in Biomechanics and Mechanobiology. Springer London, 2014. http://dx.doi.org/10.1007/978-1-4471-6599-6_3.
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Rapenne, Gwénaël, and Christian Joachim. "Single Rotating Molecule-Machines: Nanovehicles and Molecular Motors." In Molecular Machines and Motors. Springer International Publishing, 2014. http://dx.doi.org/10.1007/128_2013_510.
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Leigh, David A., Urszula Lewandowska, Bartosz Lewandowski, and Miriam R. Wilson. "Synthetic Molecular Walkers." In Molecular Machines and Motors. Springer International Publishing, 2014. http://dx.doi.org/10.1007/128_2014_546.
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Loget, Gabriel, and Alexander Kuhn. "Electrochemical Motors." In Discovering the Future of Molecular Sciences. Wiley-VCH Verlag GmbH & Co. KGaA, 2014. http://dx.doi.org/10.1002/9783527673223.ch14.
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Bressloff, Paul C. "Polymers and Molecular Motors." In Interdisciplinary Applied Mathematics. Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-08488-6_4.
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Lee, Hyung, and Michael Plamann. "Microtubules and Molecular Motors." In Biology of the Fungal Cell. Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-662-06101-5_11.
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Silvi, Serena, and Alberto Credi. "Molecular Motors and Machines." In Nanotechnology for Biology and Medicine. Springer New York, 2011. http://dx.doi.org/10.1007/978-0-387-31296-5_4.
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Hashidzume, Akihito, Hiroyasu Yamaguchi, and Akira Harada. "Cyclodextrin-Based Molecular Machines." In Molecular Machines and Motors. Springer International Publishing, 2014. http://dx.doi.org/10.1007/128_2014_547.
Full textConference papers on the topic "Molecular motors"
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Axelrod, Jeremy J., G. Edward Marti, and Steven Chu. "A microscope for observing intracellular transport with molecular resolution on molecular timescales." In Frontiers in Optics. Optica Publishing Group, 2024. https://doi.org/10.1364/fio.2024.jtu7b.4.
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We demonstrate an optical microscope that localizes gold nanoparticles to under 1 nm in 10 µs with illumination conditions compatible with live cell imaging. This enables molecular-scale measurements of molecular motor dynamics in intracellular transport.
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Nam, Woochul, and Bogdan I. Epureanu. "Collective Transport by Multiple Molecular Motors." In ASME 2012 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/detc2012-71226.
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Kinesin is a processive molecular motor that transports various cellular cargoes by converting chemical energy into mechanical movements. Although the motion of a single molecule has been characterized in several studies, the dynamics of collective transports remains unresolved. Since the fluctuating load acting on each motor is an important factor in the collective transport, the relation between the varying force and the chemical reaction of kinesin is considered using a stochastic mechanistic model. Several metrics are developed to measure the correlation among the motion of the motors, the force distribution, and the power loss. It is shown that both large external load and stiff cargo linkers cause highly correlated motions of motors. However, these correlated motions do not lead to faster collective transport.
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Simmel, Friedrich C., and Bernard Yurke. "DNA molecular motors." In SPIE's 8th Annual International Symposium on Smart Structures and Materials, edited by Anna-Maria R. McGowan. SPIE, 2001. http://dx.doi.org/10.1117/12.429683.
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Feringa, Ben L. "Molecular switches and motors." In NOBEL SYMPOSIUM 153: NANOSCALE ENERGY CONVERTERS. AIP, 2013. http://dx.doi.org/10.1063/1.4794713.
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LIPOWSKY, REINHARD. "MOVEMENTS OF MOLECULAR MOTORS." In Proceedings of the First Workshop. WORLD SCIENTIFIC, 2001. http://dx.doi.org/10.1142/9789812811301_0005.
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van Delden, Richard A. "Light-Driven Molecular Motors." In ELECTRIC PROPERTIES OF SYNTHETIC NANOSTRUCTURES: XVII International Winterschool/Euroconference on Electronic Properties of Novel Materials. AIP, 2004. http://dx.doi.org/10.1063/1.1812136.
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Andrews, David L., Luciana C. Dávila Romero, Jamie M. Leeder, and Matt M. Coles. "Optomechanical control of molecular motors." In SPIE NanoScience + Engineering, edited by Kishan Dholakia and Gabriel C. Spalding. SPIE, 2010. http://dx.doi.org/10.1117/12.860641.
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Harada, Takahiro. "Phenomenological Energetics for Molecular Motors." In ISIS INTERNATIONAL SYMPOSIUM ON INTERDISCIPLINARY SCIENCE. AIP, 2005. http://dx.doi.org/10.1063/1.1900404.
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Lipowsky, Reinhard, and Steffen Liepelt. "Molecular motors and stochastic networks." In Stochastic Models in Biological Sciences. Institute of Mathematics Polish Academy of Sciences, 2008. http://dx.doi.org/10.4064/bc80-0-9.
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Enomoto, Akihiro, Michael J. Moore, Tadashi Nakano, and Tatsuya Suda. "Stochastic cargo transport by molecular motors in molecular communication." In ICC 2012 - 2012 IEEE International Conference on Communications. IEEE, 2012. http://dx.doi.org/10.1109/icc.2012.6364950.
Full textReports on the topic "Molecular motors"
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Li, Quan. Light-Driven Chiral Molecular Motors for Passive Agile Filters. Defense Technical Information Center, 2014. http://dx.doi.org/10.21236/ada605831.
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Montemagno, Carlo. Development of a Generator to Power ATP-Driven Molecular Motors. Office of Scientific and Technical Information (OSTI), 2002. http://dx.doi.org/10.2172/900245.
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Schiefelbein, J. Molecular genetics of myosin motors in Arabidopsis. Final report, July 1, 1992--June 30, 1996. Office of Scientific and Technical Information (OSTI), 1997. http://dx.doi.org/10.2172/486111.
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Satir, Peter. Motor Molecule Long Term Survival in Motility Devices. Defense Technical Information Center, 2007. http://dx.doi.org/10.21236/ada473607.
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Duke, Joseph R., Robert B. Funchess, and Frank D. Blum. Molecular Motions of the Head Group of SHBS in Lamellar Liquid Crystals. Defense Technical Information Center, 1991. http://dx.doi.org/10.21236/ada243499.
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Frontiera, Renee. Determination of Vibrational Motions Driving Photoinduced Electron Transfer Reactions in Molecular Crystals and Organic Thin Films. Office of Scientific and Technical Information (OSTI), 2017. http://dx.doi.org/10.2172/2315605.
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Rafaeli, Ada, Wendell Roelofs, and Anat Zada Byers. Identification and gene regulation of the desaturase enzymes involved in sex-pheromone biosynthesis of pest moths infesting grain. United States Department of Agriculture, 2008. http://dx.doi.org/10.32747/2008.7613880.bard.
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The original objectives of the approved proposal included: 1. Establishment of the biosynthetic pathways for pheromone production using labeled precursors and GC-MS. 2. The elucidation of a circadian regulation of key enzymes in the biosynthetic pathway. 3. The identification, characterization and confirmation of functional expression of the delta-desaturases. 4. The identification of gene regulatory processes involved in the expression of the key enzymes in the biosynthetic pathway. Background to the topic: Moths constitute one of the major groups of pest insects in agriculture and their reproductive behavior is dependent on chemical communication. Sex-pheromone blends are utilized by a variety of moth species to attract conspecific mates. The sex pheromones used are commonly composed of blends of aliphatic molecules that vary in chain length, geometry, degree and position of double bonds and functional groups. They are formed by various actions of specific delta-desaturases to which chain shortening, elongation, reduction, acetylation, and oxidation of a common fatty acyl precursor is coupled. In most of the moth species sex-pheromone biosynthesis is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). The development of specific and safe insect control strategies utilizing pheromone systems depends on a clear knowledge of the molecular mechanisms involved. In this proposal we aimed at identifying and characterizing specific desaturases involved in the biosynthetic pathway of two moth pest-speciesof stored products, P. interpunctella and S. cerealella, and to elucidate the regulation of the enzymes involved in pheromone biosynthesis. Due to technical difficulties the second stored product pest was excluded from the study at an early phase of the research project. Major conclusions: Within the framework of the planned objectives we confirmed the pheromone biosynthetic pathway of P. interpunctella and H. armigera by using labeled precursor molecules. In addition, in conjunction with various inhibitors we determined the PBAN-stimulated rate-limiting step for these biosynthetic pathways. We thereby present conclusive evidence that the enzyme Acetyl Coenzyme A Carboxylase is activated as a result of PBAN stimulation. We also found that P. interpunctella produce the main pheromone component Z9, E12 Tetradecenyl acetate through the action of a D11 desaturase working on the 16:Acid precursor. This is evidenced by the high amount of incorporation of ²H-labeled 16:Acid into pheromone when compared to the incorporation of ²H-labeled 14:Acid. However, in contrast to reports on other moth species, P. interpunctella is also capable of utilizing the 14:Acid precursor, although to a much lesser extent than the 16:Acid precursor. Despite the discovery of nine different desaturase gene transcripts in this species, from the present study it is evident that although PCR detected all nine gene transcripts, specific to female pheromone glands, only two are highly expressed whereas the other 7 are expressed at levels of at least 10⁵ fold lower showing very low abundance. These two genes correspond to D11-like desaturases strengthening the hypothesis that the main biosynthetic pathway involves a D11 desaturase.
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Rafaeli, Ada, and Russell Jurenka. Molecular Characterization of PBAN G-protein Coupled Receptors in Moth Pest Species: Design of Antagonists. United States Department of Agriculture, 2012. http://dx.doi.org/10.32747/2012.7593390.bard.
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The proposed research was directed at determining the activation/binding domains and gene regulation of the PBAN-R’s thereby providing information for the design and screening of potential PBAN-R-blockers and to indicate possible ways of preventing the process from proceeding to its completion. Our specific aims included: (1) The identification of the PBAN-R binding domain by a combination of: (a) in silico modeling studies for identifying specific amino-acid side chains that are likely to be involved in binding PBAN with the receptor and; (b) bioassays to verify the modeling studies using mutant receptors, cell lines and pheromone glands (at tissue and organism levels) against selected, designed compounds to confirm if compounds are agonists or antagonists. (2) The elucidation ofthemolecular regulationmechanisms of PBAN-R by:(a) age-dependence of gene expression; (b) the effect of hormones and; (c) PBAN-R characterization in male hair-pencil complexes. Background to the topic Insects have several closely related G protein-coupled receptors (GPCRs) belonging to the pyrokinin/PBAN family, one with the ligand pheromone biosynthesis activating neuropeptide or pyrokinin-2 and another with diapause hormone or pyrokinin-1 as a ligand. We were unable to identify the diapause hormone receptor from Helicoverpa zea despite considerable effort. A third, related receptor is activated by a product of the capa gene, periviscerokinins. The pyrokinin/PBAN family of GPCRs and their ligands has been identified in various insects, such as Drosophila, several moth species, mosquitoes, Triboliumcastaneum, Apis mellifera, Nasoniavitripennis, and Acyrthosiphon pisum. Physiological functions of pyrokinin peptides include muscle contraction, whereas PBAN regulates pheromone production in moths plus other functions indicating the pleiotropic nature of these ligands. Based on the alignment of annotated genomic sequences, the primary and secondary structures of the pyrokinin/PBAN family of receptors have similarity with the corresponding structures of the capa or periviscerokinin receptors of insects and the neuromedin U receptors found in vertebrates. Major conclusions, solutions, achievements Evolutionary trace analysisof receptor extracellular domains exhibited several class-specific amino acid residues, which could indicate putative domains for activation of these receptors by ligand recognition and binding. Through site-directed point mutations, the 3rd extracellular domain of PBAN-R was shown to be critical for ligand selection. We identified three receptors that belong to the PBAN family of GPCRs and a partial sequence for the periviscerokinin receptor from the European corn borer, Ostrinianubilalis. Functional expression studies confirmed that only the C-variant of the PBAN-R is active. We identified a non-peptide agonist that will activate the PBAN-receptor from H. zea. We determined that there is transcriptional control of the PBAN-R in two moth species during the development of the pupa to adult, and we demonstrated that this transcriptional regulation is independent of juvenile hormone biosynthesis. This transcriptional control also occurs in male hair-pencil gland complexes of both moth species indicating a regulatory role for PBAN in males. Ultimate confirmation for PBAN's function in the male tissue was revealed through knockdown of the PBAN-R using RNAi-mediated gene-silencing. Implications, both scientific and agricultural The identification of a non-peptide agonist can be exploited in the future for the design of additional compounds that will activate the receptor and to elucidate the binding properties of this receptor. The increase in expression levels of the PBAN-R transcript was delineated to occur at a critical period of 5 hours post-eclosion and its regulation can now be studied. The mysterious role of PBAN in the males was elucidated by using a combination of physiological, biochemical and molecular genetics techniques.
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McElwain, Terry F., Eugene Pipano, Guy H. Palmer, Varda Shkap, Stephn A. Hines, and Wendy C. Brown. Protection of Cattle against Babesiosis: Immunization against Babesia bovis with an Optimized RAP-1/Apical Complex Construct. United States Department of Agriculture, 1999. http://dx.doi.org/10.32747/1999.7573063.bard.
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Previous research and current efforts at control of babesiosis fall short of meeting the needs of countries where the disease is endemic, such as Israel, as well as the needs of exporting countries and countries bordering on endemic areas, such as the U.S. Our long-term goal is to develop improved methods of immunization against bovine babesiosis based on an understanding of the molecular mechanisms of immune protection and parasite targets of a protective immune response. In our previous BARD project, we established the basis for focusing on rhoptry antigens as components of a subunit vaccine against bovine babesiosis, and for additional research to better characterize rhoptry associated protein-1 (RAP-1) as a target of protective immunity. In this continuation BARD project, our objectives were to [1] optimize the immune response against RAP-1, and [2] identify additional rhoptry candidate vaccine antigens. The entire locus encoding B. bovis RAP-1 was sequenced, and the rap-1 open reading frame compared among several strains. Unlike B. bigemina, in which multiple gene copies with variant domains encode RAP-1, the B. bovis RAP-1 locus contains only two identical genes which are conserved among strains. Through testing of multiple truncated constructs of rRAP-1, one or more immunodominant T cell epitopes were mapped to the amino terminal half of RAP-1. At least one linear and one conformational B cell epitope have been demonstrated in the same amino terminal construct, which in B. bigemina RAP-1 also contains an epitope recognized by neutralizing antibody. The amine terminal half of the molecule represents the most highly conserved part of the gene family and contains motifs conserved broadly among the apicomplexa. In contrast, the carboxy terminal half of B. bovis RAP-1 is less well conserved and contains multiple repeats encoding a linear B cell epitope potentially capable of inducing an ineffective, T cell independent, type 2 immune response. Therefore, we are testing an amino terminal fragment of RAP-1 (RAP-1N) in an immunization trial in cattle. Cattle have beer immunized with RAP-1N or control antigen, and IL-12 with Ribi adjuvant. Evaluation of the immune response is ongoing, and challenge with virulent B. bovis will occur in the near future. While no new rhoptry antigens were identified, our studies did identify and characterize a new spherical body antigen (SBP3), and several heat shock proteins (HSP's). The SBP3 and HSP21 antigens stimulate T cells from immune cattle and are considered new vaccine candidates worthy of further testing. Overall, we conclude that a single RAP-1 vaccine construct representing the conserved amino terminal region of the molecule should be sufficient for immunization against all strains of B. bovis. While results of the ongoing immunization trial will direct our next research steps, results at this time are consistent with our long term goal of designing a subunit vaccine which contains only the epitopes relevant to induction of protective immunity. Parallel studies are defining the mechanisms of protective immunity. Apicomplexan protozoa, including babesiosis and malaria, cause persistent diseases for which control is inadequate. The apical organelles are defining features of these complex protozoa, and have been conserved through the evolutionary process, Past and current BARD projects on babesiosis have established the validity and potential of exploiting these conserved organelles in developing improved control methods applicable to all apicomplexan diseases.
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Rafaeli, Ada, Russell Jurenka, and Chris Sander. Molecular characterisation of PBAN-receptors: a basis for the development and screening of antagonists against Pheromone biosynthesis in moth pest species. United States Department of Agriculture, 2008. http://dx.doi.org/10.32747/2008.7695862.bard.
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The original objectives of the approved proposal included: (a) The determination of species- and tissue-specificity of the PBAN-R; (b) the elucidation of the role of juvenile hormone in gene regulation of the PBAN-R; (c) the identificationof the ligand binding domains in the PBAN-R and (d) the development of efficient screening assays in order to screen potential antagonists that will block the PBAN-R. Background to the topic: Moths constitute one of the major groups of pest insects in agriculture and their reproductive behavior is dependent on chemical communication. Sex-pheromone blends are utilised by a variety of moth species to attract conspecific mates. In most of the moth species sex-pheromone biosynthesis is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). In order to devise ideal strategies for mating disruption/prevention, we proposed to study the interactions between PBAN and its membrane-bound receptor in order to devise potential antagonists. Major conclusions: Within the framework of the planned objectives we have confirmed the similarities between the two Helicoverpa species: armigera and zea. Receptor sequences of the two Helicoverpa spp. are 98% identical with most changes taking place in the C-terminal. Our findings indicate that PBAN or PBAN-like receptors are also present in the neural tissues and may represent a neurotransmitter-like function for PBAN-like peptides. Surprisingly the gene encoding the PBAN-receptor was also present in the male homologous tissue, but it is absent at the protein level. The presence of the receptor (at the gene- and protein-levels), and the subsequent pheromonotropic activity are age-dependent and up-regulated by Juvenile Hormone in pharate females but down-regulated by Juvenile Hormone in adult females. Lower levels of pheromonotropic activity were observed when challenged with pyrokinin-like peptides than with HezPBAN as ligand. A model of the 3D structure of the receptor was created using the X-ray structure of rhodopsin as a template after sequence alignment of the HezPBAN-R with several other GPCRs and computer simulated docking with the model predicted putative binding sites. Using in silico mutagenesis the predicted docking model was validated with experimental data obtained from expressed chimera receptors in Sf9 cells created by exchanging between the three extracellular loops of the HezPBAN-R and the Drosophila Pyrokinin-R (CG9918). The chimera receptors also indicated that the 3ʳᵈ extracellular loop is important for recognition of PBAN or Diapause hormone ligands. Implications: The project has successfully completed all the objectives and we are now in a position to be able to design and screen potential antagonists for pheromone production. The successful docking simulation-experiments encourage the use of in silico experiments for initial (high-throughput) screening of potential antagonists. However, the differential responses between the expressed receptor (Sf9 cells) and the endogenous receptor (pheromone glands) emphasize the importance of assaying lead compounds using several alternative bioassays (at the cellular, tissue and organism levels). The surprising discovery of the presence of the gene encoding the PBAN-R in the male homologous tissue, but its absence at the protein level, launches opportunities for studying molecular regulation pathways and the evolution of these GPCRs. Overall this research will advance research towards the goal of finding antagonists for this important class of receptors that might encompass a variety of essential insect functions.