src homology 3 [SH3] domain

Introduction

The src homology 3 (SH3) domain is a group of related sequences 50-100 amino acids in length orginally found in regulatory regions of nonreceptor tyrosine kinases. SH3-domain is found independent of SH2 in several cytoskeletal proteins.

The c-abl protein associates with actin through its SH3-domain. SH3 binds with specificity to proline-rich motifs. 2 conserved aromatic residues are involved in binding. with specificity conferred by neighboring residues.

In vitro, SH3-domains bind to proline-rich peptides of approximately 10 amino acid residues in length with Kd's of 5-100 uM. Peptides binding SH3-domains adopt a left-handed polyproline type-2 helix with 3 residues/turn & contain the consensus X-P-p-X-P, where X tends to be aliphatic & the 2 conserved prolines (P) are essential for high-affinity binding. The intervening scaffolding residue (p) tends to be proline. A residue such as Arg, N- or C-terminal to the X-P-p-X-P consensus, may participate in a salt-bridge with a residue such as Glu in the SH3-domain.

Peptides that bind SH3-domains may do so in either of 2 orientations. The SH3-domain functions largely to colocalize proteins associating through SH3-proline rich interactions. Proteins with SH3-domains are closely tied to control of cell morphology.

More general terms

• domain
• binding site
• cytoplasmic motif

Additional terms

• proline-rich region
• src homology 2 [SH2] domain
• src proto-oncogene protein