Solution Structure of the Ubiquitin-Binding Domain in Swa2p from Saccharomyces cerevisiae

Nicholas Chim, Walter E. Gall, Jing Xiao, Mark P. Harris, Todd R. Graham, Andrzej M. Krezel

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The SWA2/AUX1 gene has been proposed to encode the Saccharomyces cerevisiae ortholog of mammalian auxilin. Swa2p is required for clathrin assembly/dissassembly in vivo, thereby implicating it in intracellular protein and lipid trafficking. While investigating the 287-residue N-terminal region of Swa2p, we found a single stably folded domain between residues 140 and 180. Using binding assays and structural analysis, we established this to be a ubiquitin-associated (UBA) domain, unidentified by bioinformatics of the yeast genome. We determined the solution structure of this Swa2p domain and found a characteristic three-helix UBA fold. Comparisons of structures of known UBA folds reveal that the position of the third helix is quite variable. This helix in Swa2p UBA contains a bulkier tyrosine in place of smaller residues found in other UBAs and cannot pack as close to the second helix. The molecular surface of Swa2p UBA has a mostly negative potential, with a single hydrophobic surface patch found also in the UBA domains of human protein, HHR23A. The presence of a UBA domain implicates Swa2p in novel roles involving ubiquitin and ubiquitinated substrates. We propose that Swa2p is a multifunctional protein capable of recognizing several proteins through its protein-protein recognition domains.

Original languageEnglish
Pages (from-to)784-793
Number of pages10
JournalProteins: Structure, Function and Genetics
Volume54
Issue number4
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Keywords

  • Auxilin
  • NMR
  • Swa2p
  • Ubiquitin
  • Ubiquitin-associated domain

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