Institut de Biologie StructuraleGrenoble / France


09/12/2015 - Large Scale Conformational Dynamics Control the Function of H5N1 Influenza Polymerase
An international collaboration of scientists from the IBS (FDP group), the EMBL and the ILL has revealed the molecular function of a protein essential for replication of H5N1 influenza virus. Scientists used a combination of solution-state NMR, small-angle neutron scattering, small-angle X-ray scattering (SAXS), and Förster resonance energy transfer (FRET) to reveal structural changes in the 627-NLS domain of the Influenza A RNA polymerase. This domain is able to adopt two very different conformations, adjustable according to the needs of the virus. Depending on the temperature, this protein assumes a ‘close state’, allowing the polymerase to run and the viral proteins to be synthesized, or an ‘open-form’ observed here for the first time, giving its ability to interact with other proteins and thus allowing entry in infected cell nucleus. Switching from one conformation to another enables an essential part of the polymerase to enter the nucleus of the infected cell, where the viral genome is replicated. This study illustrates how the conformational flexibility of a protein allows it to adapt its function, facilitating infection of the host.
Press release

08/10/2015 - New light on transit into and out of the nucleus of the cell
The essential mechanism by which molecules are transported into the nucleus of the cell has been revealed by an international collaboration implicating researchers at the Institut de Biologie Structurale (Grenoble), the EMBL (Heidelberg), the Heidelberg Insitute of Theoretical Studies, and the University of Cambridge. Combining in vitro and in vivo experimental observations and simulation, the consortium was able to demonstrate how nucleoporins, highly flexible proteins present in the pores of the nuclear envelope, create a selective barrier by exploiting multiple, weak interactions with the transporting proteins, allowing for rapid but selective passage into the nucleus.
Press release

05/10/2015 - Molecules can still move, even inside crystals
X-ray crystallography reveals the three-dimensional structure of a molecule, especially for therapeutic or biotechnological purposes. For the first time, a study has shown that residual movements continue to animate proteins inside a crystal and that this movement ’blurs’ the structures obtained via crystallography. The study stresses that the more these residual movements are restricted, the better the crystalline order.
Press release (in french only)

06/05/2015 - Versatile Switch for Light-Controlled Cells

Scientists from IBS, Jülich, Frankfurt and Moscow uncovered the atomic structure of KR2, a light-driven transporter for sodium ions which had only recently been discovered. Based on the structural information the team then identified a simple way to turn KR2 from a sodium- into a potassium pump using simple means.
Integrated into neurons, this could make KR2 a valuable tool for optogenetics, a new field of research that uses light-sensitive proteins as molecular switches to precisely control the activity of neurons and other electrically excitable cells using light impulses.
Press release

30/04/2015 - Direct observation of hierarchical protein dynamics
Proteins are complex machines that are in constant motion, moving continuously in order to carry out their functions. Their multiple component atoms also have their individual motion patterns, making the entire protein a system of non-stop highly complex movement. Understanding how a protein moves is the key to developing drugs that can efficiently interact with it. But because of its complexity, protein motion has been notoriously difficult to study. Scientists at IBS-Grenoble, EPFL and ENS-Lyon, have developed a new method for studying protein motion by first freezing proteins and then slowly “waking them up” with increasing temperature.
Press release

27/04/2015 - Alzheimer’s disease markers could be identified through protein water mobility
A study of the water mobility on the surface of tau protein fibres has been conducted by a global team of scientists using neutron scattering experiments at the Institut Laue-Langevin (ILL) in Grenoble, France and the Jülich Centre for Neutron Science at the Heinz Maier-Leibnitz-Zentrum (MLZ) in Garching, Germany. The IBS scientists (from the Dynamics and kinetics of molecular processes Group) found water mobility on the surface of tau protein fibres is increased; the findings suggest that the movement of water molecules could be a marker for the presence of amyloid tau fibres and contribute to the detection of Alzheimer’s disease.
Press release

16/04/2015 - How water molecules dance to activate proteins
An international team of researchers from the IBS (DYNAMOP group), the Institut Laue-Langevin, the Forschungszentrum Jülich, the University of California Irvine, the Australian Institute of Science and Technology Organisation, the Max Planck Institute Mülheim and the University of Perugia has shed light on the molecular mechanism behind the importance of water for functional protein dynamics. The scientists have discovered that water’s ability to flow on the surface of proteins makes them sufficiently dynamic to be biologically active.
Press release

29/01/2015 - Visualizing the Molecular Recognition Trajectory of an Intrinsically Disordered Protein
For the first time, IBS researchers observed at atomic scale the trajectory and successive changes of shape of a viral disordered protein, from its free state to its attachment to another viral protein.The approach of this study, providing high-resolution structural and kinetic information about a complex folding and binding interaction trajectory, can be applied to a number of experimental systems to provide a general framework for understanding conformational disorder in biomolecular function and could lead to the development of innovative anti-viral.
Press release (in french only)