title: Ubiquitin binds to and regulates a subset of SH3 domains.
abstract: SH3 domains are modules of 50-70 amino acids that promote interactions among proteins, often participating in the assembly of large dynamic complexes. These domains bind to peptide ligands, which usually contain a core Pro-X-X-Pro (PXXP) sequence. Here we identify a class of SH3 domains that bind to ubiquitin. The yeast endocytic protein Sla1, as well as the mammalian proteins CIN85 and amphiphysin, carry ubiquitin-binding SH3 domains. Ubiquitin and peptide ligands bind to the same hydrophobic groove on the SH3 domain surface, and ubiquitin and a PXXP-containing protein fragment compete for binding to SH3 domains. We conclude that a subset of SH3 domains constitutes a distinct type of ubiquitin-binding domain and that ubiquitin binding can negatively regulate interaction of SH3 domains with canonical proline-rich ligands.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Svetoslava D
authors.initials: SD
authors.lastname: Stamenova
authors.forename: Michael E
authors.initials: ME
authors.lastname: French
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.forename: Smitha A
authors.initials: SA
authors.lastname: Francis
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Kramer
authors.forename: Linda
authors.initials: L
authors.lastname: Hicke
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004705:Endocytosis; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008024:Ligands; D011994:Recombinant Proteins; C082265:SLA1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin