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SH3 Protein Domain

Pro-rich Sequence Binding: SH3 Domain

The C-terminal SH3 domain of SEM-5 bound to mSOS peptide (red).

Domain Binding and Function

Src-homology 3 (SH3) domains bind to Pro-rich peptides that form a left-handed poly-Pro type II helix, with the minimal consensus Pro-X-X-Pro. An aliphatic residue usually precedes each proline, with each of the aliphatic-Pro pairs binding to a hydrophobic pocket on the SH3 domain. In principle, the ligand can bind in either orientation. An additional non-Pro residue (frequently Arg) contacts the SH3 domain and can form part of the binding core. Such peptides usually bind to the SH3 domain with a Kd in the µM range. The binding affinity and specificity can be markedly increased by tertiary interactions involving loops on the SH3 domain.

Structure Reference

  1. Lim, W.A. et al. (1994) Nature 372(6504), 375–379.

Examples of Domain Proteins

Pro-rich Sequence Binding: SH3 Domain

Binding Examples

SH3 Domain Proteins Binding Partners SH3 Domain Binding Sites
Src Tyrosine Kinase p85 subunit of Pl3 kinase RPLPVAP Class l N-terminal to C-terminal binding site
Crk Adaptor Protein C3G guanidine nucleotide exchanger PPPALPPKKR Class ll C-terminal to N-terminal binding site