Interactions between SH2 and SH3 domains

Src homology 2 (SH2) and SH3 domains are abundant protein and peptide binding modules in signalling molecules. Certain SH2 and SH3 domains have been shown to form functional and physical interactions. The structural basis of dimer formation was studied by docking three dimensional structures of the domains and by analysing structural and functional properties of the dimers. The experimentally verified dimers were noticed to have very large buried surfaces, extensive hydrogen bonding networks, and complementary surfaces, properties which are characteristic for protein-protein interactions. The number of hydrogen bonds between the domains is exceptionally high for interacting protein pairs. Also the buried accessible surface is large, especially when considering the small size of the domains. The dimer results were used to describe mutation information in structural terms and to discuss regulation of protein tyrosine kinases.