Piet Gros studies the molecular mechanisms of recognition and regulation that underlie biological processes. His major expertise is in the area of protein crystallography methodology and its application to large human plasma proteins and cell-surface receptors and membrane proteins.
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. His research goal is to reveal the mechanisms of tertiary and quaternary-induced activation in multi-domain proteins and multi-protein complexes that underlie the recognition and regulation processes.
Key research results include structural studies of (i) complement proteins and complexes, which have revealed the molecular mechanisms that underlie key steps in the human immune defense by the complement system, (ii) adhesion of von Willebrand factor (A1 domain) to its platelet receptor GpIb and (iii) several bacterial outer-membrane proteins involved in pathogenicity. Piet Gros collaborates 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.
Piet Gros is extremely grateful for the many excellent contributions of the PhD students, post-doctoral fellows and technicians in his lab.
- EMBO member (since 2013)
- Knight in the Order of the Netherlands Lion (Ridder in de Orde van de Nederlandse Leeuw; since 2013).
- Spinoza prize of the Netherlands Organisation for Scientific Research, NWO (2010).
- Member of the Royal Academy of Arts and Sciences, KNAW (since 2010).
- ERC Advanced Grant, EU (2008).
- E.J. Cohn lecturer, IDI Harvard Medical School USA (2008).
- Pionier Award, Council for Chemical Sciences, NWO-CW (2000).
- Young Chemist Awards, Council for Chemical Sciences, NWO-CW (1997 and 1999).
- Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5. W.C. Peng*, W. de Lau*, F. Forneris, J.C.M. Granneman, M. Huch, H. Clevers and P. Gros, Cell Reports 3, 1885-1892 (2013). *These authors contributed equally.
- Modelling dynamics in protein crystal structures by ensemble refinement. B.T. Burnley, P.V. Afonine, P.D. Adams and P. Gros, eLife 1:e00311. doi: 10.7554/elife.00311. (2012).
- Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9. M.A. Hadders*, D. Bubeck*, P. Roversi, S. Hakobyan, F. Forneris, B.P. Morgan, M.K. Pangburn, O. Llorca, S.M. Lea and P. Gros, Cell Reports 1, 200-207 (2012). *These authors contributed equally.
- 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).