title: Binding of a proline-independent hydrophobic motif by the Candida albicans Rvs167-3 SH3 domain.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Areti
authors.initials: A
authors.lastname: Gkourtsa
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Janny
authors.initials: J
authors.lastname: van den Burg
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Teja
authors.initials: T
authors.lastname: Avula
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Hochstenbach
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Electronic address: b.distel@amc.uva.nl.
authors.forename: Ben
authors.initials: B
authors.lastname: Distel
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000201:enzymology*; D004252:DNA Mutational Analysis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011392:Proline / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D005656:Fungal Proteins; D014364:Tryptophan; D011392:Proline
keywords: Candida albicans; Non-canonical ligand; Proline-independent binding; Rvs167-3; SH3 domain