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Conformational dynamics of proteins in the solid state

Objective

Conformational dynamics are intimately linked to the biological activity of proteins, thereby regulating the essential processes of life. In particular protein motion plays an essential role in catalysis, allowing conformational rearrangements to align key catalytic amino acids and in ligand binding allowing the entry of co-factors into areas that would otherwise be inaccessible. Mobility also plays a major role in the thermodynamic stability of functional states; in molecular recognition processes that often involve disorder-to-order transitions; and in allostery and molecular signalling, where correlated molecular motions can transmit information between distant sites in a protein. Dynamic transitions also mediate the onset of pathological malfunction and disease. NMR spectroscopy is uniquely suited to study a large number of these dynamic processes, resolving detailed and important site-specific information about motions spanning a vast range of time scales in both folded and unfolded proteins, and in both the liquid and the solid phase. We believe that the key to understanding the complex relationship between protein dynamics and molecular function and malfunction requires an accurate description of the behavior of proteins in their different phases and forms, and an understanding of the transition between different states. In this study we are interested in developing a self-consistent framework for measuring and describing protein dynamics in the solid state. To this end in this project we propose to develop a number of NMR methods extending substantially the scope of accessible protein motions in solids. This work is a part of concerted collaborative effort that couples for the first time NMR data from both solid and solutions with complementary data from elastic incoherent neutron scattering and molecular simulation in order to provide a general consistent picture of dynamical processes in proteins.

Call for proposal

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

ECOLE NORMALE SUPERIEURE DE LYON
Address
46 Allee D'italie
69364 Lyon
France
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 176 803,79
Administrative Contact
Valérie Tessier (Ms.)