SH3 Structure and Ligand Binding

Hie structural determination of SH3 domains with bound Pro-rich peptides has shown that the Pro-rich section of the ligand is bound as a left-handed polyproline Type 11 hehx with three amino acid residues per turn. Hie polyproline Type 11 hehx was described for polyproline some time ago. 

The sequence X-P-p-X-P is a consensus sequence for SH3 ligands, in which the two proline residues P are invariant, X is usually an aliphatic residue and p is often a Pro residue. The two invariant proline residues are each bound in a hydrophobic pocket of the SH3 domain. Peptide hgands can be bound in the C- N and also in the N- C direction. Like the SH2 domains, there are many different SH3 domains. The different SH3 domains demonstrate differing binding preferences for Pro-rich sequences, the specificity being determined by the neighboring residues of the invariant proline. 

---