Research group of Piet Gros
Prof.Dr. Piet Gros
Member of the Royal Netherlands Academy of Arts and Sciences (KNAW); Recipient of the Spinoza award (2010)
E-mail: p.gros @ uu.nl
My research group uses protein crystallography to study bio-molecular recognition and regulation processes with emphasis on bio-medically important proteins, in particular in the area of infection and immunity. Regulation in cells and organisms is achieved by the interplay of proteins acting in concert to achieve a control over time and space. In many cases, the proteins involved are multi-domain proteins that function in large complexes. This enables a collective set of proteins to form a protein machinery that carries out elementary regulatory functions such as initiation, amplification, localization and inhibition. Our goal is to reveal the mechanisms of tertiary and quaternary-induced activation in multi-domain proteins and multi-protein complexes that underlie these recognition and regulation processes.
Over the last few years we have mainly focused on infection and immunity, in particular (1) the immune response by the complement system and complement-evasion mechanisms of pathogens and (2) outer-membrane proteins of pathogenic bacteria. We collaborate with national and international biomedical and biological research groups in these areas. The projects provide a structural basis for host-pathogen interactions and for understanding molecular disorders in diseases, which is crucial for structure-based approaches to develop novel drugs and vaccines.
In addition, we remain to have a keen interest in crystallographic methodology with respect to the phase problem and structure refinement.
Structures of C3b in complex with factors B and D give insight into complement convertase formation, F. Forneris, D. Ricklin, J. Wu, A. Tzekou, R.S. Wallace, J. Lambris and P. Gros, Science 330, 1816-1920 (2010).
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor, S.H.M. Rooijakkers*, J. Wu*, M. Ruyken, R. van Domselaar, K.L. Planken, A. Tzekou, D. Ricklin, J.D. Lambris, B.J.C. Janssen, J.A.G. van Strijp and P. Gros, Nature Immunology 10, 721-727 (2009).
* These authors contributed equally.
Structure of complement fragment C3b-factor H and implications for host protection by complement regulators, J. Wu, Y.-Q. Wu, D. Ricklin, B.J.C. Janssen, J.D. Lambris and P. Gros, Nature Immunology 10, 728-733 (2009).
Complement driven by conformational changes, P. Gros, F.J. Milder and B.J.C. Janssen, Nature Reviews Immunology 8, 48-58 (2008).
Structure of C8α-MACPF reveals mechanism of membrane attack in complement immune defense, M.A. Hadders, D.X. Beringer and P. Gros, Science 317, 1552-1554 (2007).
Factor B structure provides insights into the activation of the central protease of the complement system, F.J. Milder, L. Gomes, A. Schouten, B.J.C. Janssen, E.G. Huizinga, R.A. Romijn, W. Hemrika, A. Roos, M.R. Daha and P. Gros, Nature Structural and Molecular Biology 14, 224-228 (2007).
Structure of C3b reveals conformational changes underlying complement activity, B.J.C. Janssen, A. Christodoulidou, A. McCarthy, J.D. Lambris and P. Gros, Nature 444, 213-216 (2006).
Structures of complement component C3 provide insights in function and evolution of immunity, B.J.C. Janssen, E.G. Huizinga, H.C.A. Raaijmakers, A. Roos, M.R. Daha, K. Nilsson-Ekdahl, B. Nilsson and P. Gros, Nature 437, 505-511 (2005).
Structure of the translocator domain of a bacterial autotransporter, C.J. Oomen, P. van Ulsen, P. van Gelder, M. Feijen, J. Tommassen and P. Gros, EMBO Journal 23, 1257-1266 (2004).
Structures of Glycoprotein Ibα and its complex with von Willebrand Factor A1 domain, E.G. Huizinga, S. Tsuji, R.A.P. Romijn, M.E. Schiphorst, Ph.G. de Groot, J.J. Sixma and P. Gros, Science 297, 1176-1179 (2002).
Crystal structure of the Outer Membrane Protease OmpT from Escherichia coli suggests a novel catalytic site, L. Vandeputte-Rutten, R.A. Kramer, J. Kroon, N. Dekker, M.R. Egmond and P. Gros, EMBO Journal 20, 5033-5039 (2001).
Specific chemical and structural damage to proteins produced by synchrotron radiation, M. Weik. R.B.G. Ravelli, G. Kryger, S. McSweeney, M.L. Raves, M. Harel, P. Gros, I. Silman, J. Kroon and J.L. Sussman, PNAS U.S.A. 97, 623-628 (2000).
Adhesion of human β2-Glycoprotein I to phospholipids based on its crystal structure, B. Bouma, Ph.G. de Groot, J.M.H. van den Elsen, R.B.G. Ravelli, A. Schouten, M.J.A. Simmelink, R.H.W.M. Derksen, J. Kroon and P. Gros, EMBO Journal 18, 5166-5174 (1999).
Crystallography and NMR System: a new software system for macromolecular structure determination, A.T. Brunger, P.D. Adams, G.M. Clore, W.L. DeLano, P. Gros, R.W. Grosse-Kunstleve, J.-S. Jiang, J. Kuszweski, M. Nilges, N.S. Pannu, R.J. Read, L.M. Rice, T. Simonson and G.L. Warren, Acta Crystallographica D54, 905-921 (1998).
Inclusion of Thermal Motion in Crystallographic Structures by Restrained Molecular Dynamics, P. Gros, W.F. van Gunsteren and W.G.J. Hol, Science 249, 1149-1152 (1990).