B.A. Biochemistry, Clark University, 1985
Research in my lab focuses on
understanding the rules that govern the recognition and assembly of
macromolecular complexes in the cell. It is clear that macromolecular
interactions are central to the proper functioning, regulation and
specificity of any cellular process, for example, signaling,
transport, and replication. I am particularly interested in the
protein-protein interactions that allow these assemblies to form in a
specific manner. I am also interested in how small ligands are able
to mediate or interfere with these interactions.
The biological system studied in this
lab involves a group of closely related members of the Ras superfamily of GTPases. The
protein-protein interactions mediating signal transduction pathways in
which these GTPases are involved result in diverse and highly spefic
biological outcomes, despite the fact that they have extremely similar
protein architecture and funtion through a common mechanism of action.
This is a system in which multiple protein-protein and protein-ligand
interactions are at the heart of important signal transduction
pathways within the cell.
The tools used to study the principles underlying specific macromolecular recognition include protein crystallography and computational biophysics. Molecular biology is used to engineer relevant constructs of the interacting proteins of interest. At the same time, we strive to give meaning to our results in the context of the cellular environment. One of the novel approaches used in this lab is the multiple solvent crystal structures (MSCS) method , developed initially using elastase as a model system.
Buhrman, G., Wink, G. and Mattos, C., "Transformation efficiency of RasQ61 mutants linked to closing of switch regions over the nucleotide", in preparation.
Mattos, C. and Clark, A. C., "Minimizing Frustration by Folding in an Aqueous Environment", Archives of Biochemistry and Biophysics, in press.
Milam, S.L., Nicely, N.I., Feeney, B., Mattos, C., Clark, A.C., "Rapid Folding and Unfolding of Apaf-1 CARD", Journal of Molecular Biology, 369:290-304 (2007).
Ringe, D. and Mattos, C., "Location of Binding Sites on Proteins by the Multiple Solvent Crystal Structure Method", Chapter in Fragment-based Approaches in Drug Discovery, Methods and Principles in Medicinal Chemistry (Jahnke, W., Erlanson, D. A., Eds) Wiley-VCH; vol 34, 67-88 (2006).
Feeney, B., Pop, C., Swartz, P., Mattos, C. and Clark, A.C., "The Role of Loop Bundle Hydrogen Bonds in the Maturation and Activity of (Pro)caspase-3", Biochemistry, 45:13249-13263 (2006).
Mattos, C., Bellamacina, C., Peisach, E., Pereira, A., Vitkup, D., Petsko, G.A. and Ringe, D., "Multiple Solvent Crystal Structures: Probing Binding Sites, Plasticity and Hydration", Journal of Molecular Biology, 357:1471-1482 (2006).
Buhrman, G., Parker, G., Sohn, J., Rudolph, J. and Mattos, C., "Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfide bond", Biochemistry, 44:5307-5316 (2005).
Nicely, N., Kosak, J., de Serrano, V., and Mattos, C., "Crystal structures of Ral-GppNHp and Ral-GDP reveal two binding sites that are also present in Ras and Rap", Structure, 12(11):2025-2036 (2004).
Mattos, C., Cohen, J.D., Green, D.F., Tidor, B., and Karplus, M., "X-ray Structural and Simulation Analysis of a Protein Mutant: The Value of a Combined Approach.", Proteins: Structure, Function, and Bioinformatics, 55(3):733-742 (2004).
Buhrman G, de Serrano V, Mattos C., "Organic Solvents Order the Dynamic Switch II in Ras Crystals.", Structure (Camb)., 11(7):747-751 (2003).
Mattos, C., "Protein-Water Interactions in a Dynamic World", Trends in Biochemical Sciences, 27(4):203-208 (2002).
Mattos, C. & Ringe, D., "Proteins in Organic Solvents." Current Opinion in Structural Biology 11:761-764 (2001).
Mattos, C. & Ringe, D., Solvent Structure, in International Tables for Crystallography (Rossman, M. G. & Arnold, E., Eds). Kluwer Academic Publishers: Dordrecht p. 623-640 (2001).
Ringe, D. & Mattos, C., "Analysis of the Binding Surfaces of Proteins", Med. Res. Rev. 19, No 4. (1999).
MacKerell Jr., A. D., Bashford, D., Bellott, M., Dunbrack Jr., R. L., Evanseck, J., Field, M. J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph, D., Kuchnir, L., Kuczera, K., Lau, F. T. K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D. T., Prodhom, B., Reiher III, W. E., Roux, B., Schlenkrich, M., Smith, J., Stote, R., Straub, J., Watanabe, M., Wiorkiewicz-Kuczera, J., Yin, D., and Karplus, M., All-atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins, J. Phys. Chem. B 102:3586-3616 (1998).
Mattos, C. and Ringe D., "Locating and Characterizing Binding Sites on Proteins" Nature Biotechnology 14:595-599 (1996).
Allen, K. N., Bellamacina, C. R., Ding, X., Jeffery, C. J., Mattos, C., Petsko, G. A., and Ringe, D., "An Experimental Approach to Mapping the Binding Surfaces of Crystalline Proteins, J. Phys. Chem. 100:2605-2611 (1996).
Mattos, C., Giammona, D., Petsko, G.A., and Ringe, D., "Structural Analysis of the Active Site of Porcine Pancreatic Elastase Based on the X-Ray Crystal Structure of Complexes with Trifluoroacetyl-Dipeptide-Anilide Inhibitors", Biochemistry 34:3193-3203 (1995).
Mattos, C., Petsko, G. A. and Karplus, M., "Analysis of Two-Residue Turns in Proteins", J. Mol. Biol. 238:733-747 (1994).
Mattos, C., Rasmussen, B., Ding, X., Petsko, G.A. & Ringe, D. "Analogous Inhibitors of Elastase Do Not Always Bind Analogously" Nature Structural Biology 1:55-58 (1994).
Mattos, C., and Ringe, D., "Multiple Binding Modes. Chapter in 3D QSAR in Drug Design -- Theory, Methods and Applications, (H. Kubinyi, ed.) ESCOM Science Publisher, Leiden (1993).