IMR Press / FBL / Volume 13 / Issue 13 / DOI: 10.2741/3053

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article

The SH3 domain- a family of versatile peptide- and protein-recognition module

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1 Department of Biochemistry and the Siebens-Drake Medical Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada

*Author to whom correspondence should be addressed.

 

Front. Biosci. (Landmark Ed) 2008, 13(13), 4938–4952; https://doi.org/10.2741/3053
Published: 1 May 2008
Abstract

Src homology 3 (SH3) domains were initially characterized as a prevalent protein module that recognizes proline-rich sequences, in particular those containing a PxxP motif. Recent studies have shown that the specificity and cellular function of SH3 domains are far more diverse than previously appreciated. Despite lacking distinguishing features, the ligand-binding surface of an SH3 domain can be molded to accommodate a variety of peptide ligands. Moreover, certain SH3 domains are capable of using surfaces distinct from the canonical ligand-binding site to engage a peptide or protein. The identification of novel motifs and domains recognized by the SH3 domain greatly expands the ligand pool and cellular function for this family. However, this also imposes the question as to how the specificity of the hundreds of human SH3 domains is regulated in a cell to ensure their proper functions. Here we review literature on the specificity of SH3 domains, with an emphasis on the structural basis of ligand recognition, and discuss mechanisms employed by SH3 domain-containing proteins to execute defined cellular functions through highly regulated SH3-ligand interactions.

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