Binding of a proline-independent hydrophobic motif by the Candida albicans Rvs167-3 SH3 domain.
Src-homology 3 (SH3) domains are small protein-protein interaction modules. While most SH3 domains bind to proline-x-x-proline (PxxP) containing motifs in their binding partners, some SH3 domains recognize motifs other than proline-based sequences. Recently, we showed that the SH3 domain of Candida albicans Rvs167-3 binds peptides enriched in hydrophobic residues and containing a single proline residue (RΦxΦxΦP, where x is any amino acid and Φ is a hydrophobic residue). Here, we demonstrate that the proline in this motif is not required for Rvs167-3 SH3 recognition. Through mutagenesis studies we show that binding of the peptide ligand involves the conserved tryptophan in the canonical PxxP binding pocket as well as residues in the extended n-Src loop of Rvs167-3 SH3. Our studies establish a novel, proline-independent, binding sequence for Rvs167-3 SH3 (RΦxΦxΦ) that is comprised of a positively charged residue (arginine) and three hydrophobic residues.
['Gkourtsa|Areti|A|', 'van den Burg|Janny|J|', 'Avula|Teja|T|', 'Hochstenbach|Frans|F|', 'Distel|Ben|B|']
D000595:Amino Acid Sequence D002176:Candida albicans D004252:DNA Mutational Analysis D005656:Fungal Proteins D008958:Models, Molecular D008969:Molecular Sequence Data D011392:Proline D011485:Protein Binding D011487:Protein Conformation D014364:Tryptophan D018909:src Homology Domains
Candida albicans Rvs167-3 SH3 domain Non-canonical ligand Proline-independent binding