Дисертації з теми "Protein LMs"
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Batzenschlager, Morgane. "Diversité fonctionnelle des protéines GIPs/MZT1 (Gamma-tubulin complex protein 3- Interacting Proteins/Mitotic spindle organiZing proTein1) à l'interface nucléo-cytoplasmique chez Arabidopsis thaliana." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ030.
Повний текст джерелаIn Arabidopsis, the nuclear envelope is a nucleation center where gamma-tubulin complexes initiate the polymerization of microtubules. Conserved from plants to humans, GIPs/MZT1 proteins were initially discovered as AtGCP3 interacting partners. Our investigations were devoted to the molecular and functional characterization of AtGIPs and their associated proteins at the nucleocytoplasmic interface. We confirmed that AtGIPs are integral components of gamma-tubulin complexes, and showed that they interact with each other, TSA1 (TonSoKu [TSK]-Associating protein 1) and centromeric histone H3 (CenH3). Genetic interactions between GIPs, TSA1 and TSK reveal severe defects at the organism, cellular and nuclear scales. gip1gip2 mutants exhibit a decrease of centromeric and pericentromeric cohesion. Altogether, this is the first evidence for the role of a gamma–tubulin complex component in the structural maintenance of centromeric regions, and in defining nuclear morphology and architecture
Ghanim, Mustafa. "Les aspects génétiques des démences frontotemporales." Paris 6, 2010. http://www.theses.fr/2010PA066039.
Повний текст джерелаGuillaud, Laurent. "Étude de la localisation et du rôle fonctionnel des protéines STOP dans les cellules neuronales." Université Joseph Fourier (Grenoble ; 1971-2015), 1998. http://www.theses.fr/1998GRE10160.
Повний текст джерелаDurand, Jean-Pierre. "Contribution a l'etude du groupe des proteines nucleaires de faible mobilite electrophoretique (lmg)." Nantes, 1988. http://www.theses.fr/1988NANT2010.
Повний текст джерелаObiol, Pardo Cristian. "Disrupting the protein-protein recognition in cancer pathways by molecular modeling." Doctoral thesis, Universitat de Barcelona, 2008. http://hdl.handle.net/10803/2759.
Повний текст джерелаOverexpression of antiapoptotic genes has been correlated with tumor growth and resistance to
chemotherapy, thus many efforts have been done to block the activity of XIAP and Survivin, central proteins acting in apoptosis and studied in the present work. Moreover, the two most active proteins detected in both the oxidative and nonoxidative branches of the pentose phosphate pathway, Glucose-6-Phosphate Dehydrogenase (G6PDH) and Transketolase (TKT), have been also selected in this thesis.
Molecular Modeling methods, covering topics in protein and peptide recognition, molecular dynamics, pharmacophore generation, database searching, docking and scoring in virtual screening and binding free energy prediction, have been applied with success to discover new active molecules inhibitors of XIAP, Survivin, G6PDH and TKT proteins.
TÍTULO: "Ruptura del reconocimiento proteína-proteína en rutas tumorales mediante modelización
molecular".
TEXTO:
El cáncer es el segunda causa de muerte por enfermedad en los paises industrializados. A pesar de la existencia de métodos eficaces de detección precoz y tratamientos cada vez más efectivos responsables de la reducción de mortalidad, algunos tipos de tumores presentan todavía tratamientos difíciles y bajos índices de supervivencia. Los fármacos convencionales sólo exhiben un índice terapéutico moderado, entre células sanas y tumorales, por ello los avances recientes se centran en encontrar tratamientos menos tóxicos para esta enfermedad. Así pues, los fármacos del futuro deberán incidir en rutas biológicas específicas, involucrando el crecimiento celular y la
proliferación descontrolada. Siguiendo este planteamiento, en este trabajo se han seleccionado dos mecanismos biológicos involucrados en el cáncer, llamados apoptosis (o muerte celular programada) y ruta de las pentosas fosfato, con el objetivo de encontrar nuevos inhibidores de las proteínas más sensibles de ambas rutas.
La sobreexpresión de genes antiapoptóticos se ha correlacionado con el crecimiento tumoral y la
resistencia a los tratamientos habituales. Así, se está trabajando en entender el funcionamiento de dos proteínas importantes de esta ruta, el XIAP y el Survivin, las cuales se han seleccionado en este trabajo, debido a que todavía no existen fármacos en el mercado que actúen sobre estas dos proteínas y debido a que su interés terapéutico se ha demostrado claramente.
Por otro lado, en este trabajo también se han estudiado las dos proteínas más activas detectadas en la rama oxidativa y no oxidativa de la ruta de las pentosas fosfato, la Glucosa-6-Fosfato Deshidrogenasa y la Transketolasa.
El objetivo principal ha consistido en aplicar métodos de la Modelización Molecular, que cubren
tópicos recientes, como el reconocimiento de péptidos y proteínas, la búsqueda en bases de datos, el anclaje y evaluación del cribado virtual de compuestos y la predicción de energías libres de unión, para encontrar nuevos inhibidores de las proteínas XIAP, Survivin, Glucosa-6-Fosfato Deshidrogenasa y Transketolasa.
Masoud, Kinda. "Caractérisation moléculaire et fonctionnelle des protéines GIPs (Gamma-tubulin complex protein 3-Interacting Proteins) d'Arabidopsis thaliana." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ011/document.
Повний текст джерелаMicrotubules (MTs) constitute one of the cytoskeletal networks in eukaryotic cells. They are involved in various processes such as cell division, intracellular transport and cell morphogenesis. In higher plants, MTs can be organized into dynamic structures, which undergo continual assembly and disassembly during the cell cycle. This specificity requires the recruitment of the nucleation complexes of the MTs to the nuclear envelope, to the cortex and to pre-existing MTs. The work of A. C. Schmit’s team (IBMP, CNRS, Strasbourg), in which I did my thesis, focuses on the characterization of MT nucleation complexes (γ-TuRCs) and the regulation of mitotic spindle assembly in plants. We have identified small proteins interacting with Gamma-tubulin Complex Protein 3 (GCP) and named GIP1 and GIP2 (GCP3-Interacting Proteins). The aim of these studies was to characterize this new class of proteins in order to understand their role. It shows that GIPs are conserved among eukaryotes and suggests that their association with the γ-TuRC participates in the regulation of their activity and the formation of a robust mitotic spindle. The localization of GIPs during the cell cycle and the phenotypes observed in T-DNA insertional gip1gip2 double mutants indicatethat GIPs are required for the recruitment of γ-TuRCs, MT nucleation, spindle assembly, cell cycle regulation and stem cell maintenance. Likewise, in vitro assays showed that GIP1 is a novel substrate for Aurora kinase1, which is a well known cell cycle regulator. The results of complementation experiments with GIP1 phosphomutants indicate that the phosphorylation of GIPs may be required for their function(s). Altogether, our results have contributed to the characterization of a new class of proteins involved in MT nucleation/organization and functions. The study of the interaction network (interactome) of GIPs and oftheir homologues could open new ways of research in the control of cell division and in the fight against cancer
Kwan, Ann Hau Yu. "Protein Design Based on a PHD Scaffold." Thesis, The University of Sydney, 2004. http://hdl.handle.net/2123/564.
Повний текст джерелаKwan, Ann Hau Yu. "Protein Design Based on a PHD Scaffold." University of Sydney. Molecular and Microbial Biosciences, 2004. http://hdl.handle.net/2123/564.
Повний текст джерелаMoser, von Filseck Joachim. "Mécanismes du transport lipidique par les protéines ORP/Osh." Thesis, Nice, 2014. http://www.theses.fr/2014NICE4138/document.
Повний текст джерелаAn uneven lipid distribution is essential for the function of eukaryotic organelles. However, exchange of material by vesicular trafficking has a tendency to perturb this distribution; mechanisms must though exist to ensure lipid homeostasis. Osh proteins (S. cerevisiae) and OSBP-Related Proteins (ORPs, H. sapiens), are lipid transfer proteins (LTPs). Osh4 is capable of exchanging ergosterol for phosphatidylinositol 4-phosphate (PI4P), found on the Golgi. Using novel fluorescent tools to measure with unprecedented precision the transport of sterol and PI4P, we find that Osh4 can transport sterol against its concentration gradient using the energy of a PI4P gradient. Coupled to phosphoinositide metabolism, this allows Osh4 to transport sterol to the trans-Golgi and create the sterol gradients observed between these organelles. OSBP participates in the creation of membrane contact sites (MCSs) via its capacity to connect ER membranes to those of the trans-Golgi. We have shown that it uses PI4P for transporting cholesterol from the ER to the trans-Golgi by sterol/PI4P counterexchange, hence also autoregulating its tethering activity. Finally, the identification of phosphatidylserine as a ligand for Osh6 allowed us to analyze the possible extrapolation of the PI4P counterexchange mechanism. We have solved the crystal structure of Osh6 in complex with PI4P and have been able to follow counterexchange of PI(4)P and PS in vitro. Concluding, our studies allow us to suggest a general mechanism for ORP/Osh-mediated counterexchange of PI4P for other lipids to maintain lipid gradients between the ER and late membranes of the secretory pathway
Cook, Neil James. "Le gmp cyclique et la phototransduction chez les vertebres." Strasbourg 1, 1986. http://www.theses.fr/1986STR13147.
Повний текст джерелаParra, Julien. "Sulfoprotéomique : développement analytique et rôle dans les processus d'interactions protéine / protéine." Thesis, Evry-Val d'Essonne, 2014. http://www.theses.fr/2014EVRY0045.
Повний текст джерелаSulfoproteomics term designs protein sulfation studies. It appears during the 2000’s, when the interest for others Post-Translational Modifications (PTMs) than phosphorylation and glycosylation was growing up. Even though sulfation is thought to be an important PTM, a weak number of publications has emerged about it, notably if we compare with the huge quantity of phosphorylation papers. This difference is mainly due to the difficulty to correctly analyze sulfated proteins and peptides in the classical ways of proteomics, as in mass spectrometry for example. The goal of this thesis is to develop mass spectrometry methods dedicated to the characterization of sulfated species, in order to improve the knowledge of this PTM. To do that, we have mainly used negative ion mode, which is almost never used, with two fragmentations techniques for the MS/MS spectra, which are CID and HCD. Results obtained allow us to pinpoint an analytical method allowing the differentiation between sulfation and phosphorylation (they are isobaric), based on the presence of specific ion for each PTM in MS/MS. In another part of the project, we have investigated the role of sulfation in the interaction between a cellular receptor, CXCR4, and its in vivo ligand, the chemokine SDF-1/CXCL12. We used capillary electrophoresis for this work, and it could be a good basis for future analyses using capillary electrophoresis coupled with mass spectrometry, in order to have a better characterization of the observed complexes
Torrent, Albertí Gerard. "L´onconasa com a model per l´estudi de les bases moleculars de la citotoxicitat de les ribonucleases pancreàtiques. Aplicacions a la construcció de ribonucleases amb activitat antimicrobiana." Doctoral thesis, Universitat de Girona, 2009. http://hdl.handle.net/10803/7636.
Повний текст джерелаThe first part of this work has been focused on the characterization and optimization of the activation process of the recombinant onconase to get an enzyme analogous to the native form. For this, Met-1 removal and Glu1 cyclization have been followed by MALDI-TOF MS. The second part of this work is focused on the study of the contribution of the 30-75 disulfide bond of onconase to its biological properties. The results suggest that the redox potential of the cytosol could reduce the disulfide bond 30-75 affecting the binding of onconase-ribonuclease inhibitor. The third part has been focused on the construction of HP-RNase and onconase variants endowed with bactericidal activity. For this, we have introduced a bactericidal (YRWR) determinant described for eosinophil cationic protein onto both enzymes. The resulting variants have bactericidal activity against gram-negative bacteria.
Di, Guilmi Anne-Marie. "Étude de l'interaction de l'adénovirus humain de sérotype 3 avec les cellules HeLa." Université Joseph Fourier (Grenoble ; 1971-2015), 1994. http://www.theses.fr/1994GRE10058.
Повний текст джерелаFalcon, de Longevialle Alexis. "Identification des protéines PPR impliquées dans l'épissage des ARN messagers dans les chloroplastes et les mitochondries chez Arabidopsis Thaliana." Thesis, Evry-Val d'Essonne, 2010. http://www.theses.fr/2010EVRY0015.
Повний текст джерелаThe RNA splicing mechanism in organelles is described to be ancestral to that of the nuclear spliceosome. However, whereas this last complex is well known, only very few splicing factors have been identified and characterized in chloroplasts and mitochondria. Many RNA binding proteins have acquired roles in RNA splicing, and indeed a variety of often unrelated RNA binding proteins have essential functions in splicing of many plastid introns in plants, with varying degrees of specificity. The largest family of RNA binding proteins in plant organelles is the pentatricopeptide repeat (PPR) family. PPR proteins are involved in diverse post-transcriptional processes in organelles. In 2006, among hundreds of higher plant proteins of this family, only one was described as being required for a splicing event - PPR4 was shown to be absolutely and specifically required for the trans-splicing of the rps12 intron 1 in plastids (Schmitz-Linneweber et al., 2006). The main purpose of this PhD thesis was to characterize other PPR proteins involved in this process. By using a reverse genetics approach and by developing tools for the detection of splicing defects, seven new PPR proteins involved in RNA splicing of a subset of chloroplast or mitochondria introns have been characterized. In parallel, in order to characterize proteins involved in PPR-containing complexes, a TAP-TAG approach has been carried out on a few PPR proteins involved in splicing or editing of organellar RNA. The identification of partner proteins of 3 PPR proteins allows us to draw new mechanistic models and new hypotheses. Finally, the final part of the manuscript describes the discovery of splicing isoforms of PPR-encoding mRNAs. Alternative splicing may be involved in regulation of PPR gene expression and/or in increasing the diversity of the PPR protein family
Rosell, Oliveras Mireia. "Application of computational docking to the characterization and modulation of protein-protein interactions of biomedical interest." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/673607.
Повний текст джерелаEl estudio de los detalles estructurales en 3D de las interacciones de proteínas es esencial para comprender las funciones biomoleculares a nivel molecular. En este contexto, la disponibilidad limitada de estructuras experimentales de complejos proteína-proteína en resolución atómica está impulsando el desarrollo de métodos de acoplamiento computacional que apuntan a complementar la cobertura estructural actual de interacciones de proteínas. Uno de estos enfoques de acoplamiento es pyDock, que utiliza van der Waals, electrostática y energía de desolvatación para puntuar las poses de acoplamiento generadas por una variedad de métodos de muestreo, generalmente FTDock o ZDOCK. El método ha demostrado un rendimiento de predicción consistentemente bueno en experimentos de evaluación de toda la comunidad como CAPRI o CASP, y ha proporcionado conocimientos biológicos e interpretación profunda de experimentos al modelar muchas interacciones biomoleculares de interés biomédico y biotecnológico. Aquí, describimos nuestro enfoque utilizando pyDock para el modelado estructural de ensamblajes de proteínas y la aplicación de sus módulos a diferentes fenómenos de reconocimiento biomolecular, como el modelado del modo de unión, la interfície y la predicción de puntos calientes, el uso de restricciones basadas en datos experimentales, la inclusión de datos estructurales de baja resolución, estimación de afinidad de unión o modelado de ensamblajes homo- y hetero- oligoméricos. La integración de enfoques de acoplamiento ab initio y basados en plantillas está emergiendo como la estrategia óptima para modelar complejos de proteínas y ensamblajes multimoleculares. Revisaremos los nuevos avances metodológicos sobre el acoplamiento ab initio y el modelado integrativo. La séptima edición de CAPRI impuso nuevos desafíos al modelado de complejos proteína-proteína, como la oligomerización multimérica, las interacciones proteína-péptido y proteína-oligosacárido. Muchos de los objetivos propuestos necesitaban la integración eficiente de acoplamiento de cuerpo rígido, modelado basado en plantillas, optimización flexible, puntuación multiparamétrica y restricciones experimentales. Esto fue especialmente relevante para los conjuntos multimoleculares propuestos en las rondas conjuntas CASP13-CAPRI46. Presentaremos los resultados para la séptima edición de CAPRI y la Ronda 46 de CAPRI, el tercer desafío de predicción del ensamblaje de proteínas CASP-CAPRI conjunto. Uno de los efectos potenciales conocidos de las sustituciones de aminoácidos que causan enfermedades en las proteínas es modular las interacciones proteína-proteína (PPI). Para interpretar tales variantes a nivel molecular y obtener información útil con fines de predicción, es importante determinar si están ubicadas en interfaces proteína-proteína, que se componen de dos regiones principales, núcleo y borde, con diferente conservación evolutiva y diferentes propiedades fisicoquímicas. En la tesis, hemos realizado un análisis estructural, energético y computacional de interacciones entre proteínas que albergan mutaciones relacionadas con enfermedades detectadas en el cribado neonatal. Los residuos de interfície se clasificaron como núcleo o borde, lo que demuestra que los residuos del núcleo son los que más contribuyen a la energía libre de unión del PPI. Es más probable que las variantes que causan enfermedades se produzcan en la región del núcleo de la interfície que en el borde de la interfície de la proteína (p <0,0001). Por el contrario, las variantes neutrales se encuentran más a menudo en el borde de la interfície o en la superficie que no interactúa en lugar de en la región del núcleo de la interfície. También encontramos que la arginina, el triptófano y la tirosina están sobrerrepresentados entre los residuos mutados que conducen a la enfermedad. Estos resultados pueden mejorar nuestra comprensión de las enfermedades a nivel molecular y, por lo tanto, contribuir a la medicina personalizada al ayudar a los médicos a proporcionar diagnósticos y tratamientos adecuados. Los efectos fenotípicos de variaciones genéticas no-sinónimas que conducen o predisponen a la enfermedad pueden racionalizarse sobre la base del impacto funcional y estructural en la proteína mutada, incluida la perturbación de la red de interacción y las vías moleculares en las que participa dicha proteína. Por lo tanto, comprender estos efectos a nivel molecular es esencial para construir modelos de enfermedad precisos y lograr una mayor precisión en el diagnóstico y la intervención terapéutica. En este contexto, podemos caracterizar computacionalmente el efecto de mutaciones patológicas en interacciones proteína-proteína específicas ("edgetic"), en base a su estructura proteica, si está disponible, o en modelos de acoplamiento. Las interacciones proteína-proteína que están claramente estabilizadas o desestabilizadas por estas mutaciones pueden ser objetivos potenciales para la intervención terapéutica. Hemos analizado el efecto energético predicho de las mutaciones en los PPI aplicando una variedad de métodos informáticos para modelar la mutación y calcular el cambio en la afinidad de unión (FoldX, mCSM, pyDock combinados con SCWRL3). Validamos el impacto energético predictivo a través de mutaciones experimentales contenidas en SKEMPI 2.0 y aplicamos estos enfoques en variantes patológicas y neutrales de un solo aminoácido (SAV en inglés) posteriormente (de ClinVar / Humsavar y gnomAD). En base a esto, hemos identificado mutaciones patológicas que inciden claramente en las interacciones analizadas estabilizándolas o desestabilizándolas. Como se ha discutido, las interacciones proteína-proteína son importantes para procesos biológicos y situaciones patológicas y son objetivos atractivos para el descubrimiento de fármacos. Sin embargo, el diseño racional de fármacos dirigidos a las interacciones proteína-proteína sigue siendo un gran desafío. Los residuos de puntos calientes se consideran la mejor opción para apuntar a tales interacciones, pero su identificación requiere una caracterización estructural y energética detallada, que solo está disponible para una pequeña fracción de interacciones de proteínas. Esta tesis doctoral cubre una variedad de métodos computacionales que han sido reportados para el análisis energético de interfícies proteína-proteína en la búsqueda de puntos calientes y el modelado estructural de complejos proteína-proteína por acoplamiento. Esto puede ayudar a racionalizar el descubrimiento de inhibidores de moléculas pequeñas de interfícies proteína-proteína de interés terapéutico. El análisis computacional y el acoplamiento pueden ayudar a localizar la interfície, la dinámica molecular se puede utilizar para encontrar cavidades adecuadas y las predicciones de puntos calientes pueden enfocar la búsqueda de inhibidores de interacciones proteína-proteína. Una dificultad importante para aplicar métodos racionales de diseño de fármacos a las interacciones proteína-proteína es que en la mayoría de los casos no se dispone de la estructura compleja. Afortunadamente, el acoplamiento computacional puede complementar los datos experimentales. Un aspecto interesante para explorar en el futuro es la integración de estas estrategias para apuntar a las interacciones proteína-proteína con análisis mutacionales a gran escala.
Anquetil-Behra, Carole. "Les protéines de choc thermique chez les mammifères." Paris 5, 1992. http://www.theses.fr/1992PA05P203.
Повний текст джерелаVilela, Belmiro. "Functional and molecular characterization of maize open stomata 1 protein kinase." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/96978.
Повний текст джерелаLa sequía es actualmente el factor abiótico más limitante para el crecimiento de las plantas y se está agravando con los actuales cambios climáticos, aumento de población y reducción de las reservas de agua. Se estima que en el 2050 el 50% de las tierras cultivadas tengan problemas de salinidad o sequía. Por ello, la intensificación de la agricultura y el desarrollo de la mejora biotecnológica de adaptación al estrés son áreas que tienen que reforzarse. En esta tesis se pretende ampliar los conocimientos sobre la respuesta del maíz a la sequía haciendo un estudio profundizado de una quinasa de tipo SnRK2, designada ZmOST1 que está implicada en la respuesta de las plantas al déficit hídrico. - Capítulo 1: Caracterización bioquímica de la quinasa de maíz ZmOST1 en que se establece que ZmOST1 se localiza en el núcleo y citoplasma, se activa por ABA, es capaz de autofosforilar su centro activo y directamente interacciona con una fosfatasa ZmPP2C a través de su dominio regulador. - Capítulo 2: Caracterización fisiológica de ZmOST1. Se determinan los niveles de expresión y de actividad de la quinasa en diferentes tratamientos y estadios de desarrollo; se establece que ZmOST1 es capaz de recuperar el fenotipo de cierre estomático en mutantes OST1 de Arabidopsis; y se identifica un factor de transcripción que se caracteriza como un nuevo substrato de esta quinasa. - Capítulo 3: Se describe una nueva ruta de regulación de ZmOST1 en que esta quinasa es fosforilada por la CK2 (casein kinase 2) en el dominio regulador. Mutagenizando los residuos diana de la CK2 en la ZmOST1 lleva a una mayor acumulación, una menor degradación por el proteasoma y una hipersensibilidad a ABA.
Berger, François. "Étude et caractérisation de mécanismes suppresseurs dans les tumeurs cérébrales humaines et le cerveau non tumoral : anti-tyrosine kinase, p53 et ciblage exogène par le thymidine kinase herpétique." Université Joseph Fourier (Grenoble), 1995. http://www.theses.fr/1995GRE10109.
Повний текст джерелаBrady, John Joseph. "VAPORIZATION OF BIOLOGICAL MACROMOLECULES USING INTENSE, ULTRAFAST LASERS: MECHANISM AND APPLICATION TO PROTEIN CONFORMATION." Diss., Temple University Libraries, 2011. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/211496.
Повний текст джерелаPh.D.
This dissertation details the design and implementation of a state-of-the-art ambient trace analysis technique known as laser electrospray mass spectrometry. This novel technique utilizes an intense, nonresonant femtosecond laser pulse to transfer nonvolatile, fragile molecules into the gas phase from various substrates. The vaporized analyte is subsequently captured, solvated and ionized in an electrospray plume enabling mass analysis. Laser electrospray mass spectrometry is capable of analyzing samples in the liquid or solid states, mass spectral imaging of adsorbed molecules and detecting low vapor pressure analytes remotely. Experiments with biomolecules and pharmaceuticals, such as vitamin B12 and oxycodone, have demonstrated that the nonresonant femtosecond laser pulse allows for coupling into and vaporization of all molecules. This implies that sample preparation (elution, mixing with matrix and choosing samples with a particular electronic or vibrational transition) is not necessary, thus creating a universal mass analysis technique. Investigations using low vapor pressure molecules, such as lipids and proteins, led to the discovery that unfragmented molecules are transferred into the gas phase via a nonthermal mechanism. The laser electrospray mass spectrometry technique has allowed for the nonresonant femtosecond laser vaporization and mass analysis of trace amounts of a nitro-based explosive from a metal surface. The vaporization of unfragmented explosive molecules from a surface facilitates the identification of the explosive, reducing the probability of false positives and false negatives. In addition, this "soft" vaporization of molecules using nonresonant femtosecond laser pulses allows for protein to be transferred from the condensed phase into the gas phase without altering the molecule's structure, enabling ex vivo conformational analysis and possible disease typing.
Temple University--Theses
Cussac, Didier. "Les protéines G substrats des toxines bactériennes dans l'hypophyse antérieure, rôles des protéines G hétérotrimériques et des petites protéines G de la famille RHO dans les processus sécrétoires." Paris 11, 1994. http://www.theses.fr/1994PA11T021.
Повний текст джерелаGiraudon--Colas, Gaël. "Caractérisation multiéchelle d'assemblages d'hémoglobine : de l'adsorption sur les nanoparticules aux gels nanocomposites Protein−Nanoparticle Interactions: What Are the Protein−Corona Thickness and Organization? In Situ Analysis of Weakly Bound Proteins Reveals Molecular Basis of Soft Corona Formation." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASF011.
Повний текст джерелаNanocomposite protein gels are still an underdeveloped subject in the literature despite many applications ranging from enzyme immobilization to prostheses to food gels. The protein ensures the gel biocompatibility while the addition of the nanoparticles will modulate the gel mechanical properties. We decided to focus on chemically cross-linked hemoglobin gels doped with nanoparticles. Hemoglobin (Hb) was chosen for its high abundance and its oxygen binding properties. The gels will be obtained by crosslinking with glutaraldehyde (GTA), a very reactive dialdehyde. The gels will be doped with silica nanoparticles (NP) in order to understand the effect of doping with model nanoparticles on the gel. The first part of the work will focus on the hemoglobin adsorption on silica nanoparticles in order to resolve the remaining unknowns on this phenomenon, which has already been studied. The adsorption isotherms as well as the activity of the adsorbed hemoglobin will be measured. The structures of the heme, globin and the Hb/NP assembly will be studied in details. Subsequently, works will focus on gels without and with nanoparticles in order to respectively elucidate the effects of gelation and doping. We will determine the concentrations of Hb, GTA and NP to obtain a gel. Then, as with the Hb/NP assemblies, we will look at the activity and structure of Hb (heme and globin).The structuring of the gel will also be studied. Works on the gel elastic properties will also be carried out and we will finish on the dynamics of the gelled protein. When possible, the concentration effect for the different components will be determined. For all these studies, a large panel of conventional technics to characterize proteins or gels was used. Many experiments have been performed in synchrotrons and neutron research centers (radiation scattering, X-ray absorption spectroscopy, circular dichroism). Electronic paramagnetic resonance, rheology or electron microscopy, which are more accessible technics have also been employed. The most innovative aspects of this work were the effect of adsorption on heme and the understanding of the gelled protein structure, two aspects that had not been addressed until now
Malkin, Douglas Scott, and Douglas Scott Malkin. "An Investigation of a Novel Monolithic Chromatography Column, Silica Colloidal Crystal Packed Columns." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/193936.
Повний текст джерелаPigault, Claire. "Photochimie du tryptophane en absence d'oxygene : mecanisme de photejection d'electron, photodegradation dans les proteines." Université Louis Pasteur (Strasbourg) (1971-2008), 1986. http://www.theses.fr/1986STR13190.
Повний текст джерелаTuladhar, Kapil. "Lim-only domain proteins in developmental haematopoiesis." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:d6b73e89-7095-402f-9d9f-4d7837a4db00.
Повний текст джерелаWilson, Flore Adjélé. "Étude du mécanisme de photoprotection lié à l’Orange Carotenoid Protein et ses homologues chez les cyanobactéries." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS503/document.
Повний текст джерелаPhotosynthetic organisms use light energy from the sun in order to perform photosynthesis and to convert solar energy into chemical energy. Absorbance of excess light energy beyond what can be consumed in photosynthesis is dangerous for these organisms. Reactive oxygen species (ROS) are formed at the reaction centers and collecting light antennas inducing photooxidative damage which can lead to cell death. In cyanobacteria, one of these photoprotective mechanisms consists to reduce the amount of energy arriving to the reaction centers by thermal dissipation of the excess absorbed energy. Energy dissipation is accompanied by a decrease of Photosystem II-related fluorescence emission called non-photochemical quenching (NPQ). The soluble Orange Carotenoid Protein (OCPo) is essential for this photoprotective mechanism. The OCP is the first photo-active protein with a carotenoid known as light intensity sensor and acts as energy quencher of the phycobilisome (PB), the extra-membrane antenna of cyanobacteria. Structural changes occur when the OCPo absorbs a strong blue-green light leading to a red active form (OCPr). The N-terminal domain of OCPr burrows into the two external trimers of the core basal APC cylinders of the PB and increases thermal energy dissipation at the level of antenna. The OCP has an additional function in photoprotection as oxygen singlet quencher protecting cells from oxidative stress. Under low light conditions, to recover the full antenna capacity, a second protein is needed, the "Fluorescence Recovery Protein" (FRP), whose role is to detach the OCPr from the PB and accelerate its conversion into an inactive OCPo. In this manuscript, I will review the knowledge about the OCP, since the discovery of the mechanism and its characterization to the latest advances on the OCP-related-NPQ mechanism in cyanobacteria
SCHIPPERS, PIERRE-FRANCOIS. "Facteurs de variation des proteines plasmatiques chez les patients de reanimation." Aix-Marseille 2, 1992. http://www.theses.fr/1992AIX20087.
Повний текст джерелаLorenzi, Magali. "Etude des transitions structurales dans les protéines flexibles par marquage de spin suivi par spectroscopie de Résonance Paramagnétique Electronique (RPE)." Thesis, Aix-Marseille 1, 2011. http://www.theses.fr/2011AIX10139/document.
Повний текст джерелаThe study of structural transitions in proteins is of crucial interest because these transformations are involved in many biological processes. Such structural phenomena can be the source of remarkable properties in flexible or disordered proteins, properties hardly accessible by conventional structural techniques. Site-directed spin labeling combined with electron paramagnetic resonance spectroscopy (EPR) is a technique well suited for the study of these structural transitions. The insertion of a nitroxide reagent on a cysteine, natural or introduced by site-directed mutagenesis, located in a key position of a protein provides local information on possible structural changes induced by the addition of a partner. This technique was applied on two biological systems with a different degree of flexibility. The flexibility of NarJ, a chaperon protein involved in the biogenesis of the complex nitrate reductase of Escherichia coli was studied in the presence of its peptide partner. These studies enabled us to determine the interaction site and to show that the association of the two partners induced a locked conformation of NarJ. The second system is the CP12 protein of Chlamydomonas reinhardtii, involved in the regulation of a supramolecular complex of the Calvin cycle. CP12 shares some similarities with the intrinsically disordered protein but having natural and functional cysteines. The conventional labeling allowed us to highlight a new role of its partner and to demonstrate that CP12 remains disordered in the complex. Moreover, this protein was used as a model system to develop a new labeling strategy on tyrosine and to demonstrate its feasibility
Maurier, Florence. "Etude de la signalisation en aval du complexe ras-gap ; caracterisation du role de g3bp et sam68, deux proteines liant les acides nucleiques." Paris 11, 1997. http://www.theses.fr/1997PA11T033.
Повний текст джерелаPOSTEL, PATRICK. "Interet du profil proteique dans les infections genitales hautes." Amiens, 1988. http://www.theses.fr/1988AMIEM027.
Повний текст джерелаSeaayfan, Elie. "Régulation du contrôle de qualité de NKCC2 par les interactions protéine-protéine." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB026.
Повний текст джерелаThe kidney-specific Na + -K + -2C1 co-transporter, sensitive to bumetanide, NKCC2, plays an essential role in the body's fluid, electrolyte and acid-base homeostasis. Mutations of NKCC2 cause antenatal type 1 Bartter syndrome, a life-threatening kidney disease characterized by arterial hypotension associated with electrolyte abnormalities. In contrast, an increase in NKCC2 activity is associated with salt-sensitive hypertension. Yet the mechanisms underlying the regulation of NKCC2 trafficking in renal cells are scarcely known. The aim of this work was to identify the protein partners involved in the regulation of the expression and the intracellular trafficking of NKCC2, specifically in the quality control of this co-transporter. Using the yeast tow-hybrid system, we identified OS-9 as a specific binding partner of NKCC2. Lectin OS-9 is a key factor in the regulation of protein quality control at ER. Co-immunoprecipitation assay in renal cells showed that OS-9 interacts mainly with NKCC2 immature forms. Accordingly, immunocytochemistry analysis showed co-localization of the proteins mainly in the ER. Overexpression of OS-9 decreased the total abundance of NKCC2. This effect is abolished following the inhibition of the proteasome protein degradation pathway by MG132. In addition, the pulse-chase and cycloheximide-chase assays demonstrated that the marked reduction in the co-transporter protein levels was essentially due to increased protein degradation of NKCC2 immature forms. Conversely, knock-down endogenous of OS-9 increased the expression of the co-transporter by increasing the stability of its immature form. Finally, inactivation of the Mannose 6-phosphate Receptor Homology domain had no effect on its action on NKCC2, while mutation of the two NKCC2 N-glycosylation sites abolished the effect of OS- 9. In summary, our results demonstrate the involvement of lectin OS-9 in the ERAD of NKCC2. The second part of this work focused on the identification of new molecular mechanisms involved in Bartter Syndrome. We found that MAGE-D2 mutations caused X-linked new and severe form of antenatal Bartter's syndrome, characterized by a very early polyhydramnios with a high risk of premature delivery and mortality. We have shown that MAGE-D2 abnormalities lead to a lack of maturation and membrane expression of NKCC2 as well as that of the Na-Cl co-transporter, NCC, of the distal tubule. In vitro comparison of the wild-type and mutated MAGED2 interactome revealed that wild-type MAGE-D2 interacts specifically with DNAJB1 (HSP40) and / or GNAS, suggesting involvement of these two protein partners in NKCC2 and NCC regulation by MAGE-D2 during pregnancy. The third part of this work focused on the study of the effect of DNAJB1 / HSP40, partner of MAGE-D2, on the expression of NKCC2. HSP40 was also identified as a specific binding partner of NKCC2 by the yeast two-hybrid system realized by our team. We have shown that HSP40 and its co-chaperone HSPA1A (HSP70) interact with the immature form of NKCC2 at the ER. The co-expression of HSP40 and HSP70 increased the expression of NKCC2 by increasing its stability and maturation. In addition, these two co-chaperones regulate the expression of NCC in the same way. These findings suggest that MAGE-D2 cooperates with DNAJB1 / HSP40 and HSPA1A / HSP70 to protect NKCC2 and NCC against retention and degradation of NKCC2 at ER during pregnancy, revealing a new pathway for regulating NKCC2 and NCC intracellular trafficking. A better understanding of NKCC2 and NCC regulatory pathways would help to better understand the pathophysiology of sodium retention and ultimately would provide a new target for a pharmaceutical approach to preventing and / or treating kidney disease related to sodium balance
MEUNIER, XAVIER. "Les enveloppes corneocytaires et leur analyse." Strasbourg 1, 1992. http://www.theses.fr/1992STR15004.
Повний текст джерелаGERARD, PIERRE-EMMANUEL. "Les syndromes d'insulinoresistance extreme : recherche de mutations sur les genes des recepteurs de l'insuline et les transporteurs de glucose glut-4." Nice, 1993. http://www.theses.fr/1993NICE6546.
Повний текст джерелаTaha, Mohammed. "L'utilisation de cellules natural killer (NK) comme outil thérapeutique : étude clinique de phase 1 de perfusion de cellules NK du donneur après HSCT : Annexe : Pumilio 2, une protéine de liaison à l'ARN surexprimée dans les cellules NK de patients atteints de LAM, réprime les fonctions des cellules NK." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0233.
Повний текст джерелаNatural killer (NK) cells are effector lymphocytes of the innate immune system that have the ability to kill transformed cells. They play a critical role in hematological malignancies surveillance, however, tumor cells develop immunosuppressive mechanisms to escape NK cell-mediated killing. So, maintaining or improving NK cell performance is considered a major challenge. Our goals are to evaluate the impact of activated NK cells infusion on the recovery and biology of circulating NK cells post allo-SCT.Three different doses (dose 1: 106 NK cell/Kg, n=3; dose 2: 5x106 NK cell/Kg, n=7; dose 3: >5x106 NK cell/Kg, n=6) of ex-vivo IL-2 activated NK cells were infused into patients with hematological malignancies after all-SCT. Our results showed higher frequency of NK cells in the periphery of patients treated with larger doses of activated NK cells. Although the notable immature phenotype shortly after treatment, the circulating NK cells in patients receiving larger doses of activated NK cells displayed more activation status with improved maturation profile after 6 months of treatment. We also found that the expression of activating NK receptors (NKG2D, NKp30, and NKp46) augmented on circulating CD56dim NK cells of patients receiving larger doses of activated NK cells. Moreover, these cells showed a significant increase in degranulation capacity as well as cytokine secretion (IFN-Ƴ and TNF-α) throughout study period. In conclusion, we hypothesize that infusion of high-dose of ex-vivo activated NK cells could be associated with improvements of NK cell phenotype and function during immune reconstitution after allo-SCT
Shukat, Rizwan. "Contribution des nanostructures dans les agrégats protéiques et d’émulsions stabilisées par des protéines en vue de la protection de vitamine." Thesis, Paris, AgroParisTech, 2012. http://www.theses.fr/2012AGPT0042.
Повний текст джерелаWe investigated effects of processing conditions for the preparation of protein aggregates and protein-stabilized lipid droplets, as matrix carriers of sensitive lipophilic bioactive compounds, with α-tocopherol as a model. Protein-based matrices were formed from whey protein concentrate (6 wt% WPC, pH 6.5 and 65 to 75°C), in presence or absence of 4% α-tocopherol. Mixing the protein solutions without or with α-tocopherol (65°C for 15 min) led to changes in particle surface charges (from -42 to -51 mV) and sizes (from 183 to 397 nm). These parameters decreased more under further high pressure homogenisation at 1200 bar than 300 bar, in parallel with increased vitamin protection over 8 week's storage. Molecular mechanisms involved in formation of corresponding α-tocopherol-loaded protein matrix were described on the basis of heat- and high-pressure-induced whey protein denaturation and aggregation, as evidenced by differential scanning calorimetry (DSC), spectrofluorescence, multi-light scattering and SDS-PAGE electrophoretic patterns. Lipid-based matrices were developed from aqueous phases (80 wt%) containing WPC (6 wt% or 3 wt%) and lipid phases (20 wt%) in presence or absence of lecithins and/or 4% α-tocopherol, and by using a first dispersion step (65°C for 15 min) followed with HPH at 300 or 1200 bar. Our results showed that increasing HPH was accompanied by formation of lipid nanoparticles with decreasing size and protein surface concentration with an increase in α-tocopherol degradation (up to 15 wt% for 1200 bar). DSC in scanning and isothermal modes showed that reduction in lipid droplet size was accompanied by retardation in crystalline fat development under storage at 4°C, with further reduction in crystalline fat development along with further increase in supercooling for lipid droplets containing α-tocopherol. Fat polymorphism observed using time-resolved synchrotron X-ray scattering at wide and small angles (WAXS and SAXS) coupled with DSC, showed co-existence of 2Lα, 2Lβ' and 2Lβ polymorphs in all the emulsions, but at different proportions. It was observed that 2Lβ polymorphs were more prominent in lipid droplets with lower size and containing α-tocopherol in presence of lecithins that were shown to present the lowest long-term stability of α-tocopherol against chemical degradation
Dorantes, gilardi Rodrigo. "Bio-mathematical aspects of the plasticity of proteins." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAM092/document.
Повний текст джерелаProteins are biological objects made to resist perturbations and, atthe same time, adapt to new environments and new needs. What are thestructural properties of proteins allowing such plasticity? To tacklethis question we first model protein structure as a network of aminoacids and atoms in interaction. Given the 3D structural conformationof a mutation obtained In Silico, a network approachallows the quantification of its structural change. Using large setsof mutations, we concluded that structural change is independent fromthe type of amino acid replaced, or replacing after mutation. Lookingat the composition of amino acid neighborhoods, we noticed that thelocation of a type of amino acid in the 3D structure is arbitrary:meaning that constraints of amino acid interactions in a proteinshow to be position independent. Leading to theobservation that the position of the amino acid in the sequence is thesingle property modulating structural plasticity.The fact that amino acids can replace each other atany position because the interaction constraint is not dependent on thetype of amino acid,is based on the customization of neighbors via alternative amino acidmutations or compensatory mutations. Even if there is a large mutationtolerance based on structural robustness, mutations can have an impact onthe structural plasticity because of the change in strength of pairwsie interactionsand the distribution of atoms and neihgbors surrounding residues.The direct consequence of such a variable atomic packingdistribution, is a difference of void (empty space,no atoms) on the surface of residues as identified by some of my data/results.This raises the possibility that structural plasticity is not onlyregulated by amino acid and atomic contacts but also by carving localvoids within the protein structure to allow atomic motionsrequired for the function of the protein. Finally, to test this hypothesis, we haveimplemented three algorithms to measure the empty space around aminoacids to look at the relation between this empty space and structural plasticity
Pascalon, Annette. "Influence des deficits energetiques et proteiques sur l'evolution de la gestation et le taux des acides amines libres chez la ratte : effets sur les concentrations de progesterone et de prolactine aux periodes critiques de la mortalite embryonnaire." Clermont-Ferrand 2, 1988. http://www.theses.fr/1988CLF21092.
Повний текст джерелаDupoux, Alban. "Rôle des inhibitors of apoptosis proteins dans les macrophages." Dijon, 2008. http://www.theses.fr/2008DIJOS071.
Повний текст джерелаCIAP1 regulates TNFR superfamily receptors signaling and NF-kB activation. CIAP1 is an ubiquitin ligase, its first identified partner is TRAF2, which is a molecular adaptator of TNF signaling pathways. In this work, we identified a role of TRAF2 during macrophage differentiation : it makes NF-kB activation possible. Then TRAF2 is degraded by the protéasome. CIAP1 stimulates TRAF2 degradation in a Golgi apparatus associated structure by ubiquitinylation and it keeps a low expression level of TRAF2 in the macrophages. TRAF2 expression inhibits cytokines secretion after CD40L stimulation of the cells. Studying cIAP1 in other macrophages functions showed that cIAP1 seems to control the cellular response to the IFN-g. IFN-g induces cIAP1 relocalization in vesicular structure. Furthermore IAPs inhibition stimulates IL-6 secretion in response to IFN-g. Otherwise specific inhibition of cIAP1 regulates phagocytosis of E. Coli or apoptotic corpses by macrophages. CIAP1 is able to interact with regulators of the organization of cytoskeleton and vesicular traffic : RhoA, Rac1 and Cdc42. This might explain the cIAP1 involvement in phagocytosis. These results demonstrated cIAP1 and TRAF2 involvement in macrophages differentiation and functions
AUGEREAU, PATRICK. "La regulation de la transcription par les enhancers chez les eucaryotes : etude in vivo et in vitro." Université Louis Pasteur (Strasbourg) (1971-2008), 1986. http://www.theses.fr/1986STR13119.
Повний текст джерелаCORNELIS, LERAT FRANCOISE. "Analyse de l'expression de la proteine p53 dans les tumeurs gliales du systeme nerveux central." Reims, 1993. http://www.theses.fr/1993REIMM056.
Повний текст джерелаVERVYNCK, VIAN SABINE. "Contribution a l'etude de la reponse anticorps dirigee contre les proteines nucleaires du spermatozoide humain." Lille 2, 1991. http://www.theses.fr/1991LIL2M269.
Повний текст джерелаLafeillade, Bruno. "CISP/thrombospondine-2, une protéine synthétisée par les cellules corticosurrénaliennes en réponse à l'ACTH : étude comparative de la régulation de l'expression de CISP/TSP2 avec TSP1 et distribution tissulaire de TSP2." Université Joseph Fourier (Grenoble ; 1971-2015), 1997. http://www.theses.fr/1997GRE10084.
Повний текст джерелаCruz, Tapias Paola. "Un mécanisme de trans-méthylation entre les deux principales méthyltransférases de H3K9 SETDB1 et SUV39H1, régule l'établissement de l'hétérochromatine." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC285.
Повний текст джерелаHistone H3 lysine 9 (H3K9) methylation, which is established by the lysine methyltransferases (KMTs) SETDB1, SUV39H1, G9A and GLP, is a central epigenetic mechanism involved in cell fate regulation. In particular, H3K9 methylation is directly involved in heterochromatin formation and gene silencing. Our lab showed that the main H3K9 KMTs (SETDB1, G9A, GLP and SUV39H1) form a functional megacomplex involved in transcriptional silencing, probably via the cooperative establishment of the different H3K9 methylation levels. However, up to now, the regulation of the H3K9 KMT complexes is not fully understood. Interestingly, post-translational modifications (PTMs) have been implicated in the regulation of H3K9 KMT functions. In this, my PhD thesis aimed to decipher how methylation of SETDB1, regulates its activity (complex formation, interaction with partners, recruitment to chromatin), which ultimately could impact on heterochromatin formation, gene expression and cell fate regulation. SETDB1 is crucial during development and cellular differentiation. Moreover, SETDB1 is essential in mouse embryonic stem cells (mESCs) pluripotency and self-renewal, Setbd1 KO is lethal at the peri-implantation stage at 7.5 days postcoitum (dpc). Beside histones, SETDB1 is also able to methylate other proteins (e.g. UBF, ING2, p53). Notably, my current data show that SETDB1 undergoes (auto)methylation on the lysines K1170 and K1178 located inside its catalytic SET domain. SETDB1 and SUV39H1 coordinate the establishment and maintenance of H3K9me3 at constitutive pericentromeric heterochromatin and co-regulate many genomic targets within heterochromatin, including transposable elements, such as long interspersed nuclear elements (LINEs) and endogenous retroviruses (ERVs). Since SUV39H1 is a H3K9 tri-methyltransferase that uses H3K9me1 or H3K9me2 as a primary substrate, SETDB1 could probably provide mono- or di-methylated H3K9. Interestingly, my results point to a model in which SETDB1 auto-methylation paves the path to a subsequent trans-methylation by SUV39H1. This mechanism could regulate not only the SETDB1/SUV39H1 physical interaction (via the SUV39H1 chromodomain), but also cooperation in the establishment and maintenance of both heterochromatin blocks (large domains) and transposable elements (TEs) silencing, at least in ES cells. Thus, we would like to better understand how the crosstalk between these two key H3K9 KMTs, SETDB1 and SUV39H1, occurs in terms of interaction and recruitment to target loci
ROQUES, NICOLAS. "Les facteurs pronostiques des tumeurs vesicales superficielles : apport de la proteine p53." Toulouse 3, 1994. http://www.theses.fr/1994TOU31521.
Повний текст джерелаManes, Gae͏̈l. "Slap (Src-like adaptor protein)régulateur négatif de la croissance cellulaire induite par les tyrosine kinases." Montpellier 1, 1999. http://www.theses.fr/1999MON1T019.
Повний текст джерелаMillet, Mélanie. "Composition et mécanismes de formation des troubles physico-chimiques dans les produits cidricoles." Thesis, Rennes, Agrocampus Ouest, 2018. http://www.theses.fr/2018NSARB311/document.
Повний текст джерелаPhysico-chemical haze appearance during storage of clarified apple-based beverages is a concern for producers. These hazes are caused by interactions between several constituents of the beverage that lead to the formation of visible aggregates. This work had two main goals: analyze the composition of hazes in order to determine which families of compounds are responsible for their formation, and understand which mechanisms are involved. First, the composition of the haze gathered from three apple-based beverages (cider, apple juice and pommeau) was analyzed. The results revealed the implication of phenolic compounds and led to the hypothesis that their oxidation was probably one of the main factors responsible for haze formation. Proteins were found in quite large quantities in some apple juice hazes, which suggests their involvement in haze formation in this beverage.These two hypotheses have been verified using two model approaches: in a model pommeau and in a model apple juice. This work evidenced that different kinds of hazes exist in apple-based beverages. On the one hand, haze in pommeaux and ciders is mainly explained by procyanidin oligomers self-aggregation induced by their oxidation, with possible interactions with other beverage constituents. On the other hand, haze in some apple juices, which probably contain low polyphenol and high protein levels, is triggered by “Pathogenesis-Related Proteins” denaturation that lead to their self-aggregation, in interaction with oligomeric procyanidins
Devineau, Stéphanie. "Adsorption des protéines sur les nanomatériaux. Biochimie et physico-chimie d’un nouveau stress." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112215/document.
Повний текст джерелаNanomaterials raise new questions in environmental and human toxicology and represent a novel interface with specific properties with the biological medium. Several unknown remain to explain all the mechanisms of toxicity, especially at the molecular lever. When they enter the biological medium, nanoparticles get covered by a protein corona. This corona yields to a new “biological identity” that controls the cellular response to nanoparticles and their fate in the organism. We studied the adsorption of model proteins on nanostructured silica. The first part is dedicated to the characterization of nanoporous silica and silica nanoparticles that we used. Then the adsorption of myoglobin, hemoglobin and protein mixture from yeast cells was studied to determine the thermodynamic and physical-chemical parameters of protein adsorption on silica. The enrichment of basic residues, gathered in charge clusters, favors the adsorption of proteins by the formation of electrostatic interactions with the charged surface of silica, independently of the global charge of the protein. On the contrary, the enrichment in aromatic residues is unfavorable to protein adsorption because they form π-π interactions that rigidify the protein structure. The identification of adsorbed and non-adsorbed proteins from a complex medium could also be used for cellular toxicity studies. From the study of the structure, the dynamics and the activity of myoglobin and hemoglobin adsorbed on silica nanoparticles, we tried to define the state of an adsorbed protein. The structural study, based on circular dichroism, fluorescence, infrared, X-ray and UV-visible spectroscopy and microcalorimetry, shows a substantial partial structure loss of adsorbed proteins together with a high conformational heterogeneity, without major modifications of the heme structure. Two potential interaction sites of myoglobin with silica nanoparticles have been identified by a footprinting technique. The study of adsorbed myoglobin dynamics by elastic and inelastic neutron scattering highlighted the important decrease of protein dynamics that occurs upon adsorption. However, despite the structure loss, adsorbed metmyoglobin retains almost all of its activity of ligand binding. Unexpectedly, adsorbed hemoglobin shows an increase of its oxygen affinity and a decrease of its cooperativity, without any dissociation of the tetramer. This effect can be reproduced on human hemoglobin, cross-linked DCL hemoglobin and variant S hemoglobin. Besides, two effectors allow modulating the affinity of adsorbed hemoglobin. Despite the extent of structural and activity changes, all these modifications are entirely reversible upon desorption in soft conditions. The adsorption of hemoproteins on silica nanoparticles depicts a new sort of stress with resilience for proteins in terms of structure, dynamics and activity relationship
Ivashchenko, Stefaniia. "Rôle du désordre conformationnel dans les protéines du virus des oreillons." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAY026/document.
Повний текст джерелаMumps is a highly contagious disease caused by the mumps virus. The prevention treatment (vaccine) against it is already in the routine use. However, recent outbreaks still remain uncontrollable. Therefore, it is important to understand the molecular mechanism of the mumps virus life cycle. This virus belongs to the family of Paramyxoviridae. Its genome, negative strand non-segmented RNA is protected by the nucleoprotein (N) by forming filamentous structures called nucleocapsids. N plays an important role in viral genome synthesis. Together with the polymerase and its cofactor phosphoprotein (P) they constitute the transcription-replication machinery. Both N and P contain folded and unfolded regions. Despite mumps virus common morphology with other paramyxovirus, there are some differences. It has been proposed that P is an antiparallel oligomer with two extremities on the one side being in interaction with the structural part of N (Ncore). The function of the disordered domain (Ntail) remains unclear, as it does not seem to bind to the C-terminal part of P, as is the case for other paramyxoviruses. The role of the disordered domains of P is also not known. In this project we revealed mechanisms of interaction between different regions of N and P and we explain how disordered regions of N and P are implicated in the regulation of the complex machinery of viral replication. We used the nuclear magnetic resonance which is the most powerful method to determine structure, dynamics and potential interaction partners, and therefore, function of disordered viral proteins
CHAHDI, AHMED. "Activation des mastocytes par les peptides cationiques." Strasbourg 1, 1997. http://www.theses.fr/1997STR15093.
Повний текст джерелаSUCCO, ERIC. "Les deficits constitutionnels en inhibiteurs de la coagulation : analyse de 30 familles etudiees au centre d'exploration des pathologies hemorragiques et thrombotiques, c.h.u. timone." Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX20910.
Повний текст джерелаLescat, Laury. "Caractérisation et étude du rôle de lamp2a chez les poissons." Thesis, Pau, 2019. http://www.theses.fr/2019PAUU3014.
Повний текст джерелаChaperone-Mediated Autophagy (CMA) is a major pathway of lysosomal proteolysis recognized as a key player in the control of numerous cellular functions, and whose defects have been associated to several human pathologies, including neurodegenerative diseases, cancers and immune disorders. To date, this cellular function was presumed to be restricted to mammals and birds, due to the absence of an identifiable lysosome-associated membrane protein 2A (LAMP2A), a limiting and essential protein for CMA, in non-tetrapod species. However, we recently identified the existence of expressed sequences displaying high homology with the mammalian LAMP2A in several fish species, challenging that view and suggesting that CMA appeared much earlier during evolution than initially thought. In the present thesis, we first present new evidences about the evolutionary history of the gene LAMP2 in vertebrates. We demonstrate that LAMP2 appeared after the second whole genome duplication that occurred at the root of the vertebrate lineage approximately 500 million years ago. By using a fluorescent reporter previously used to track CMA in mammalian cells, we then revealed the existence of a CMA-like pathway in a fibroblast cell line of the fish medaka (Oryzias latipes). Finally, to address the physiological role of Lamp2a in fish, we generated, medaka knockout for the splice variant lamp2a, and found severe alterations in the intermediary metabolism, as previously demonstrated in mice deficient for CMA in liver. Altogether, our data provide the first evidence for a CMA-like pathway in fish and bring new perspectives on the use of complementary genetic models, such as zebrafish or medaka, for studying CMA in an evolutionary perspective