"Workshop V Cell Signaling Networks Presentation Title SH3 domain"
Workshop V: Cell Signaling Networks Presentation Title: SH3 domain mediated protein-protein interactions. Speaker: Brian K. Kay Institution: Argonne National Laboratory. Bioscience Division, Bldg. 202 Argonne, IL 60439 USA Abstract: Mediation of protein-protein interaction through modular binding domains, such as SH2, SH3, PTB, PDZ, WW, or EH domains, is an important mechanism for intracellular signaling. The physiological importance of one such module, the Src Homology 3 (SH3) domain, is evidenced by its presence in both the regulators and effectors of the Ras-mediated MAP kinase signaling pathway. SH3 domain-containing proteins have also been shown to function in a variety of diverse biological events including cytoskeletal organization, subcellular localization of proteins, and endocytosis. SH3 domains are known to bind to short proline-rich peptide sequences within interacting proteins. Typically, the ligands have the consensus sequence, PxxP, and adopt polyproline type II (PPII) helical structures which fit into shallow hydrophobic pockets, formed by aromatic residues on the surface of SH3 domains. Furthermore, SH3 domains bind the peptide ligands in one of two opposite orientations, N- to C-terminus or C- to N-terminus, with the orientation heavily influenced by interaction between the non-proline residues in the PPII helix and the residues flanking the main hydrophobic binding surface of the SH3 domain. In this talk, I will describe how screening phage-displayed combinatorial peptide libraries with SH3 domains can provide insight into both understanding their molecular recognition properties and the prediction of their natural cellular ligands. References: Kay, B., Williamson, M., and Sudol, M. (2000). The importance of being proline: the interaction of proline-rich motifs in signalling proteins with their cognate domains. FASEB J. 14, 231-241. Kay, B. K., Kasanov, J., Knight, S., and Kurakin, A. (2000). Convergent evolution with combinatorial peptides. FEBS Lett. 480, 55-62. Tong, A. H., Drees, B., Nardelli, G., Bader, G. D., Brannetti, B., Castagnoli, L., Evangelista, M., Ferracuti, S., Nelson, B., Paoluzi, S., Quondam, M., Zucconi, A., Hogue, C. W., Fields, S., Boone, C., and Cesareni, G. (2002). A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules. Science 295, 321-4.