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Characterization of membrane protein dynamics by hydrogen/deuterium exchange and time-resolved infrared spectroscopy, assisted by maximum entropy and Bayesian methods of analysis

Objetivo

Protein dynamics is essentially linked to protein function, aggregation, and folding. Time-resolved spectroscopy is specially suited to reveal these dynamics, counterbalancing the static pure-structural information provided by X-ray crystallographic structures. In equilibrium, protein conformation fluctuates, eventually visiting all possible higher-energy states in equilibrium with the ground state conformation. For soluble proteins the dynamics of such fluctuations have been successfully detected and characterized by hydrogen/deuterium exchange (HDX) combined with NMR spectroscopy. However, experimental limitations of NMR spectroscopy have precluded a similar level of understanding of the dynamics of membrane proteins. Proteins dynamics manifest themselves also when a fast perturbation is applied, such as when a laser pulse is applied to proteins with photocycles. Both in HDX and in perturbation experiments the time-resolved response of the system is a multi-exponential relaxation process. However, the relevant information to characterize and understand the protein dynamics is not the relaxation process itself, but the number, value, and nature (discrete/distributed) of the rate constants of the relaxation process. In this project our first goal is the improvement, development and application of maximum entropy and Bayesian methods to analyze the multi-exponential data arising in the HDX of membrane proteins, and in the photocycles of membrane proteins. Simultaneously, we will implement new experimental approaches of HDX to obtain dynamics information of membrane proteins by infrared spectroscopy, and apply them to at least three membrane protein systems: the melibiose transporter, bacteriorhodopsin, and a G-protein coupled receptor chimera. The combined success of both interdisciplinary goals should provide unique and fundamental information for a better understanding of membrane protein dynamics.

Convocatoria de propuestas

FP7-PEOPLE-IRG-2008
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Régimen de financiación

MC-IRG - International Re-integration Grants (IRG)

Coordinador

UNIVERSIDAD AUTONOMA DE BARCELONA
Dirección
Calle Campus Universitario Sn Cerdanyola V
08290 Cerdanyola Del Valles
España
Tipo de actividad
Higher or Secondary Education Establishments
Aportación de la UE
€ 50 000
Contacto administrativo
Esteve Padrós (Dr.)