The role of water molecules in the binding of class I and II peptides to the SH3 domain of the Fyn tyrosine kinase

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 water molecules in these protein – protein interactions. To determine whether or not the SH3 domain of the Fyn tyrosine kinase shows the same behaviour, the crystal structures of its complexes with two high-affinity synthetic peptides, VSL12 and APP12, which are class I and II peptides, respectively, have been solved. In the class I complexes two water molecules were found at the binding interface that were not present in the class II complexes. The structures suggest a role of these water molecules in facilitating conformational changes in the SH3 domain to allow the binding of the class I or II peptides. 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 water molecules involved in the binding of the peptides with previous reported hydration spots suggests a different pattern for the SH3 domains of the Src tyrosine kinase family.

Source: Acta Crystallographica Section F - August 25, 2016 Category: Biochemistry Authors: Camara-Artigas, A. Ortiz-Salmeron, E. Andujar-S á nchez, M. Bacarizo, J. Martin-Garcia, J.M. Tags: SH3 domain X-ray crystal structure Fyn tyrosine kinase proline-rich motifs research communications Source Type: research