Product(s) used in this publication: Custom Peptide Synthesis
Interactions of proline-rich motifs with SH3 domains are present in signal transduction and other important cell processes. Analysis of structural and thermodynamic data suggest a relevant role of watermolecules in these protein-protein interactions. To determine whether or not the SH3domain of the Fyntyrosinekinase shows the same behaviour, the crystal structures of its complexes with two high-affinity synthetic peptides, VSL12 and APP12, which are class I and IIpeptides, respectively, have been solved. In the class I complexes two watermolecules were found at the binding interface that were not present in the classII complexes. The structures suggest a role of these watermolecules in facilitating conformational changes in the SH3domain to allow the binding of the class I or IIpeptides. In the third binding pocket these changes modify the cation-π and salt-bridge interactions that determine the affinity of the binding. Comparison of the watermolecules involved in the binding of the peptides with previous reported hydration spots suggests a different pattern for the SH3 domains of the Src tyrosinekinase family.
Fyntyrosinekinase; SH3domain; X-ray crystal structure; proline-rich motifs