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Institut de Biologie StructuraleGrenoble / France

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

Presentation

Responsable : Martin Weik


The research objective of the team is to study the structural dynamics of various medically important proteins (e.g. involved in Alzheimer disease (AD), aging and antibiotic resistance) and the coupling to hydration water structure and dynamics. A broad range of complementary biophysical, biochemical and molecular-biology tools will be developed and applied, including neutron scattering, kinetic X-ray crystallography, microspectrophotometry, THz spectroscopy, molecular dynamics simulations, single-molecule conductance, protein deuteration and directed evolution. Our research objective includes a strong focus on ways to improve available structure-based drug design approaches.

Permanent Staff :

  • Martin Weik (CEA staff scientist)
  • Jacques-Philippe Colletier (CNRS CR2)
  • Giorgio Schiro (CNRS CR2)
  • Patrick Masson (emeritus )

Technicians :

  • Ninon Zala

Post-doctoral scientists :

  • Nicolas Coquelle
  • Eugenio Dela Mora

PhD Students :

Research topics

- Structural dynamics of acetylcholinesterase
- Structural dynamics of tau - an intrinsically unfolded protein (IUP) involved in AD
- Implication of structural dynamics in specific damage by ionizing radiation and reactive oxygen
species to proteins
- Structural dynamics and enzymatic evolution
- Structural dynamics of membrane proteins
Key words
structural dynamics of proteins, neurodegenerative diseases, acetylcholinesterase , tau protein, anti-Alzheimer drugs, reactivators of poisoned acetylcholinesterase

Specialized techniques

- Xray crystallography,
- kinetic crystallography
- neutron scattering
- microspectrophotometry

Available services

- Cryobench in crystallo spectroscopy laboratory at ESRF (A. Royant, M. Weik)

Collaborations:

- CRSSA
- ILL
- University Paris Sud
- ENS Paris
- University Rouen
- Weizmann Institute, Israel
- UCLA, USA
- UCSD, USA
- UC Irvine, USA
- Whitman College, USA
- University Oxford, UK
- University Bremen, Germany
- University Bochum, Germany
- University Groningen, The Netherlands
- University Leiden, The Netherlands
- University Siena, Italy
- University Perugia, Italy

Major publications

- Colletier, J. P., Sanson, B., Nachon, F., Gabellieri, E., Fattorusso, C., Campiani, G. & Weik, M. (2006) Conformational Flexibility in the Peripheral Site of Torpedo californica Acetylcholinesterase Revealed by the Complex Structure with a Bifunctional Inhibitor. J Am Chem Soc., 128, 4526-4527.
- Colletier, J.-P., Fournier, D., Greenblatt, H., Sussman, J.L., Zaccai, G., Silman, I. & Weik, M. (2006) Structural insights into substrate traffic and inhibition in acetylcholinesterase. EMBO J. 25, 2746-2756.
• Wood, K., Plazanet, M., Kessler, B., Gabel, F., Oesterhelt, D., Tobias, D., Zaccai, G. & Weik, M. (2007) Coupling of protein and hydration water dynamics in biological membranes. Proc. Natl. Acad. Sci. 104, 18049-18054.
- Wood, K., Frölich, A., Paciaroni, A., Moulin, M., Zaccai, G., Tobias, D. & Weik, M. (2008) Coincidence of hydration-water and soluble-protein dynamical transitions: direct measurements by neutron scattering and MD simulations. J Am Chem Soc. 130, 4586-4587.
- Colletier, J.-P., Bourgeois, D., Sanson, B., Fournier, D., Silman, I., Sussman, J.L. & Weik, M. (2008) Shoot-and-trap: use of specific X-ray damage to study structural protein dynamics by temperature-controlled cryo-crystallography. Proc. Natl. Acad. Sci. 105, 11742