Critical residues in an SH3 domain from Sem-5 suggest a mechanism for proline-rich peptide recognition

Abstract
Src homology 3 (SH3) domains bind specific proline-rich peptide motifs. To identify interactions involved in peptide recognition, we have mutated residues on the putative binding surface of an SH3 domain from the Caenorhabditis elegans protein Sem-5. Among the most critical positions are three adjacent aromatic residues, which appear to participate in highly stereospecific packing interactions with the ligand. The co-planar arrangement of two of these residues closely matches the periodicity of a poly-proline II (PPII) helix. Thus, a model for recognition has the peptide adopting a PPII helix, with the pyrrolidine rings on one helical face interlocking with the aromatic SH3 residues.