Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / BLACKLEDGE Martin

Protein Dynamics and Flexibility by NMR Group

Group leader : Martin Blackledge

Members

Permanent:

Martin Blackledge (E7 CEA)

Malene Ringkjøbing Jensen (CR2 CNRS)

Damien Maurin (Engineer CNRS)

Non-permanent:

Anton Abyzov (Ph.D. student)

Guillaume Communie (Ph.D. student)

Elise Delaforge (Ph.D. student)

Paul Guerry (Postdoctoral fellow)

Jie-rong Huang (Postdoctoral fellow)

Jaka Kragelj (Ph.D. student)

Luca Mollica (Postdoctoral fellow)

Valery Ozenne (Ph.D. student)

Robert Schneider (Postdoctoral fellow)

Presentation

Welcome to the web-page of the Protein Dynamics and Flexibility by NMR group at the IBS under the direction of Martin Blackledge.

Conformational dynamics control the biological activity of proteins, thereby regulating the essential processes of life. Protein motion plays a major role in molecular interaction, in the thermodynamic stability of functional states; in molecular recognition processes involving disorder-to-order transitions; and in allostery and molecular signalling, where correlated motions can transmit information between distant sites in a protein.

Nuclear Magnetic Resonance (NMR) spectroscopy is uniquely placed 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.

Our key research interests lie in the study of conformational flexibility in proteins in their different forms, and to further our understanding of the complex relationship between molecular motion and biological function and malfunction. Current experiments range from high resolution studies of the conformational energy landscape of folded proteins to the highly flexible behaviour of intrinsically unfolded proteins and their relationship to function.

Key Words

NMR, Conformational flexibility, Intrinsically unstructured proteins, Protein dynamics, Protein structure determination, Protein folding, Functional dynamics.

Key Publications

Intrinsic disorder in measles virus nucleocapsids. M. R. Jensen, G. Communie, E. A. Ribeiro, N. Martinez, A. Desfosses, L. Salmon, L. Mollica, F. Gabel, M. Jamin, S. Longhi, R. W. H. Ruigrok and M. Blackledge.
Proc. Natl. Acad. Sci. (U.S.A.) 108, 9839-9844 (2011).

Structure, dynamics, and kinetics of weak protein-protein complexes from NMR spin relaxation measurements of titrated solutions. L. Salmon, J. L. Ortega-Roldan, E. Lescop, A. Licinio, N. A. J. van Nuland, M. R. Jensen* and M. Blackledge*. Angew. Chem. 50, 3755-3759 (2011).

Structural biology: Proteins in dynamic equilibrium. P. Bernado and M. Blackledge. Nature 468, 1046-1048 (2010).

NMR characterization of long-range order in intrinsically disordered proteins. L. Salmon, G. Nodet, V. Ozenne, G. Yin, M. R. Jensen, M. Zweckstetter and M. Blackledge, J. Am. Chem. Soc. 132, 8407-8418 (2010).

Defining conformational ensembles of intrinsically disordered and partially folded proteins directly from chemical shifts. M. R. Jensen*, L. Salmon, G. Nodet and M. Blackledge*. J. Am. Chem. Soc. 132, 1270-1272 (2010).

Toward a unified representation of protein structural dynamics in solution. P. R. Markwick, G. Bouvignies, L. Salmon, J. A. McCammon, M. Nilges and M. Blackledge. J. Am. Chem. Soc. 131, 16968-16975 (2009).

Protein conformational flexibility from structure-free analysis of NMR dipolar couplings: quantitative and absolute determination of backbone motion in ubiquitin. L. Salmon, G. Bouvignies, P. Markwick, N. Lakomek, S. Showalter, D. W. Li, K. Walter, C. Griesinger, R. Bruschweiler and M. Blackledge. Angew. Chem. 48, 4154-4157 (2009).

Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domain. M. Wells, H. Tidow, T. J. Rutherford, P. Markwick, M. R. Jensen, E. Mylonas, D. I. Svergun, M. Blackledge* and A. R. Fersht*. Proc. Natl. Acad. Sci. (U.S.A.) 105, 5762-5767 (2008).

Highly Populated Turn Conformations in Natively Unfolded Tau Protein Identified from Residual Dipolar Couplings and Molecular Simulation. M. D. Mukrasch, P. R. L. Markwick, J. Biernat, M. von Bergen, P. Bernado, C. Griesinger, E. Mandelkow, M. Zweckstetter and M. Blackledge J. Am. Chem. Soc. 129, 5235-5243 (2007).

Exploring Multiple Timescale Motions in Protein GB3 using Accelerated Molecular Dynamics and NMR. P. Markwick, G. Bouvignies and M. Blackledge J. Am. Chem. Soc. 129, 4724-4730 (2007).

Simultaneous Determination of Protein Structure and Dynamics using Residual Dipolar Couplings. G. Bouvignies, R. Bruschweiler and M. Blackledge. J. Am. Chem. Soc. 128, 15100-15101 (2006).

A structural model for unfolded proteins from residual dipolar couplings and small angle X-ray scattering. P. Bernado, L. Blanchard, P. Timmins, D. Marion, R. Ruigrok and M. Blackledge Proc. Natl. Acad. Sci. (U.S.A.) 102, 17002-17007 (2005)

(A full publication list of the FDP group since 2000 is available here).