BernheimV1, Hal, Checkpoint, bibRecord, 000032

Investigation et caracterisation de différents homologues de transporteurs ADP/ATP

Identifieur interne : 000032 ( Hal/Checkpoint ); précédent : 000031; suivant : 000033

Investigation et caracterisation de différents homologues de transporteurs ADP/ATP

Auteurs : Aleksandra Woz Nicka-Misa Ila [France]

Source :

RBID : Hal:tel-01496246

Descripteurs français

mix :
- Cristallographie, Mitochondrie, Protéine membranaire, Structure 3D, Transport d'ADP/ATP.

English descriptors

mix :
- 3D structure, ADP/ATP transport, Crystallography, Membrane protein, Mitochondria.

Abstract

The main objective of this PhD project was to gain new structural data on the mitochondrial ADP/ATP carriers and develop tools for micro- and nano-crystallography approaches applied to membrane protein structural biology.The main role of the ADP/ATP carrier (AAC) is to import and export ADP3- and ATP4- respectively between the intermembrane space and the matrix through the inner mitochondrial membrane. AAC is the best characterized among all mitochondrial carriers. Much has been done to investigate its function and structure. However, since structural data are only available for one conformation of the protein some fundamental questions about the different conformational states adopted during the transport process still need to be answered.In this thesis we considered 4 human AAC homologs as a main target. They are involved in different genetic diseases but play also a role in cancerogenesis. This thesis describes and compares in detail the functional and structural characterization of the human AAC isoforms. It was an essential step to give insight into their native properties and is a precious starting point for the drug development field.Since the structural biology field is rapidly developing especially in serial crystallography techniques, there are more and more new applications for samples preparation, mounting and measurements in order to improve the quality of the data collected at the synchrotrons. Hence, our second objective was to use different membrane protein samples to develop new crystal-friendly crystallization set up combined with different sample environment on the beamline toward faster, more efficient and simpler data collection.

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https://tel.archives-ouvertes.fr/tel-01496246

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Links to Exploration step

Hal:tel-01496246

Le document en format XML

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<front><div type="abstract" xml:lang="en">The main objective of this PhD project was to gain new structural data on the mitochondrial ADP/ATP carriers and develop tools for micro- and nano-crystallography approaches applied to membrane protein structural biology.The main role of the ADP/ATP carrier (AAC) is to import and export ADP3- and ATP4- respectively between the intermembrane space and the matrix through the inner mitochondrial membrane. AAC is the best characterized among all mitochondrial carriers. Much has been done to investigate its function and structure. However, since structural data are only available for one conformation of the protein some fundamental questions about the different conformational states adopted during the transport process still need to be answered.In this thesis we considered 4 human AAC homologs as a main target. They are involved in different genetic diseases but play also a role in cancerogenesis. This thesis describes and compares in detail the functional and structural characterization of the human AAC isoforms. It was an essential step to give insight into their native properties and is a precious starting point for the drug development field.Since the structural biology field is rapidly developing especially in serial crystallography techniques, there are more and more new applications for samples preparation, mounting and measurements in order to improve the quality of the data collected at the synchrotrons. Hence, our second objective was to use different membrane protein samples to develop new crystal-friendly crystallization set up combined with different sample environment on the beamline toward faster, more efficient and simpler data collection.</div>
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            <abstract xml:lang="en">The main objective of this PhD project was to gain new structural data on the mitochondrial ADP/ATP carriers and develop tools for micro- and nano-crystallography approaches applied to membrane protein structural biology.The main role of the ADP/ATP carrier (AAC) is to import and export ADP3- and ATP4- respectively between the intermembrane space and the matrix through the inner mitochondrial membrane. AAC is the best characterized among all mitochondrial carriers. Much has been done to investigate its function and structure. However, since structural data are only available for one conformation of the protein some fundamental questions about the different conformational states adopted during the transport process still need to be answered.In this thesis we considered 4 human AAC homologs as a main target. They are involved in different genetic diseases but play also a role in cancerogenesis. This thesis describes and compares in detail the functional and structural characterization of the human AAC isoforms. It was an essential step to give insight into their native properties and is a precious starting point for the drug development field.Since the structural biology field is rapidly developing especially in serial crystallography techniques, there are more and more new applications for samples preparation, mounting and measurements in order to improve the quality of the data collected at the synchrotrons. Hence, our second objective was to use different membrane protein samples to develop new crystal-friendly crystallization set up combined with different sample environment on the beamline toward faster, more efficient and simpler data collection.</abstract>
            <abstract xml:lang="fr">L'objectif principal de ce projet de thèse était d'obtenir de nouvelles données structurales sur les transporteurs ADP/ATP mitochondriaux et de développer des outils pour les approches de micro- et nano-cristallographie appliquées à la biologie structurale des protéines membranaires.Le rôle principal du transporteur ADP/ATP (AAC) est d'importer et d'exporter respectivement de l’ADP3- et l’ATP4- à travers la membrane mitochondriale interne, entre l'espace intermembranaire et la matrice. AAC est le transporteur mitochondrial le mieux caractérisé de toute cette famille de protéines. De nombreuses études ont été menées pour caractériser sa fonction et sa structure. Toutefois, les données structurales n’étant disponibles que pour une conformation de la protéine, de nombreuses questions fondamentales notamment sur les différents états conformationnels adoptés par la protéine au cours du processus de transport restent encore posées. Dans cette thèse, nous avons étudié les 4 isoformes humaines d’AAC. Elles sont impliquées dans diverses maladies génétiques, mais jouent également un rôle dans la cancérogenèse. Cette thèse décrit ainsi en détail la caractérisation structurale et fonctionnelle de ces protéines et leur comparaison. C’est est une étape essentielle pour définir leurs propriétés, et constitue un point de départ précieux dans le développement de nouvelles thérapies.Le domaine de la biologie structurale ne cesse de connaître de nouveaux développements, comme c’est le cas par exemple avec l’avènement de la cristallographie sérielle. Il y a donc un besoin constant de nouvelles approches notamment pour la préparation des échantillons, leur montage sur les lignes de lumière et les collectes de données afin de continuer à améliorer la qualité des données collectées au synchrotron. Ainsi, notre objectif était d'utiliser différents échantillons de protéines membranaires pour développer de nouvelles techniques de cristallisation et de montage d’échantillons sur les lignes de lumière afin de préserver au mieux la qualité des échantillons tout en permettant des collectes de données plus rapides, plus efficaces et plus simples.</abstract>
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Investigation et caracterisation de différents homologues de transporteurs ADP/ATP

Investigation et caracterisation de différents homologues de transporteurs ADP/ATP

Source :

Descripteurs français

English descriptors

Abstract

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