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



Martin Blackledge (Research director CEA)

Malene Ringkjøbing Jensen (CR1 CNRS)

Damien Maurin (Engineer CNRS)


Anton Abyzov (Ph.D. student)

Elise Delaforge (Postdoctoral fellow)

Stefaniia Ivashchenko (Ph.D. student)

Sigrid Milles (Postdoctoral fellow)

Nicola Salvi (Postdoctoral fellow)


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

The precision with which X-ray crystallography and NMR have provided structural models of biologically active and inactive conformations of countless proteins belies an easily overlooked dilemma. Proteins are inherently dynamic, exhibiting conformational freedom on timescales from picoseconds to seconds, implicating structural rearrangements that play a major role in molecular interaction; in the thermodynamic stability of functional states; in molecular recognition processes; or in allostery and molecular signalling. Static structural models afford little insight into the underlying conformational equilibrium.

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.

The overarching interest of our research group lies in the study of protein dynamics, developing and applying diverse experimental and analytical approaches to characterize the role of conformational flexibility in biological function on a broad range of time and length scales, from molecular recognition dynamics in folded proteins, to reorganizational dynamics of large multidomain assemblies exhibiting extensive protein disorder.

Key words

NMR, conformational flexibility, intrinsically disordered proteins, protein dynamics, protein structure determination, protein folding, functional dynamics.

Key publications

J.R. Lewandowski*, M.E. Halse, M. Blackledge* and L. Emsley*.
Direct observation of hierarchical protein dynamics.
Science 348, 578-581 (2015).

J. Kragelj, A. Palencia, M.H. Nanao, D. Maurin, G. Bouvignies, M. Blackledge* and M.R. Jensen*.
Structure and dynamics of the MKK7-JNK signaling complex.
Proc. Natl. Acad. Sci. (U.S.A.) 112, 3409-3414 (2015).

R. Schneider, D. Maurin, G. Communie G, J. Kragelj, D.F. Hansen, R.W. Ruigrok, M.R. Jensen and M. Blackledge.
Visualizing the molecular recognition trajectory of an intrinsically disordered protein using multinuclear relaxation dispersion NMR.
J. Am. Chem. Soc. 137, 1220-1229 (2015).

M. Schwalbe, V. Ozenne, S. Bibow, M. Jaremko , L. Jaremko, M. Gajda, M.R. Jensen, J. Biernat, S. Becker, E. Mandelkow, M. Zweckstetter* and M. Blackledge*.
Predictive atomic resolution descriptions of intrinsically disordered hTau40 and alpha-synuclein in solution from NMR and small angle scattering.
Structure 22, 238-249 (2014).

J. Huang, L. Warner, C. Sanchez, F. Gabel, T. Madl, C. Mackereth, M. Sattler* and M. Blackledge*.
Transient electrostatic interactions dominate the conformational equilibrium sampled by multidomain splicing factor U2AF65: A combined NMR and SAXS study.
J. Am. Chem. Soc. 136, 7068-7076 (2014).

P. Guerry, L. Salmon, L. Mollica, J.L. Ortega Roldan, P. Markwick, N. van Nuland, J.A. McCammon and M. Blackledge
Mapping the population of protein conformational energy sub-states from NMR dipolar couplings.
Angew. Chem. 52, 3181-3185 (2013).

V. Ozenne, R. Schneider, M. Yao, J.R. Huang, L. Salmon, M. Zweckstetter, M.R. Jensen and M. Blackledge
Mapping the potential energy landscape of intrinsically disordered proteins at amino acid resolution.
J. Am. Chem. Soc. 134, 15138-15148 (2012).

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.
Intrinsic disorder in measles virus nucleocapsids.
Proc. Natl. Acad. Sci. (U.S.A.) 108, 9839-9844 (2011).

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

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

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

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

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

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

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

A full publication list of the FDP group since 2005 is available here.

Updated 10/02/2016 by MRJ