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- Title
Avid interactions underlie the Lys63-linked polyubiquitin binding specificities observed for UBA domains.
- Authors
Sims, Joshua J; Haririnia, Aydin; Dickinson, Bryan C; Fushman, David; Cohen, Robert E
- Abstract
Ubiquitin (denoted Ub) receptor proteins as a group must contain a diverse set of binding specificities to distinguish the many forms of polyubiquitin (polyUb) signals. Previous studies suggested that the large class of ubiquitin-associated (UBA) domains contains members with intrinsic specificity for Lys63-linked polyUb or Lys48-linked polyUb, thus explaining how UBA-containing proteins can mediate diverse signaling events. Here we show that previously observed Lys63-polyUb selectivity in UBA domains is the result of an artifact in which the dimeric fusion partner, glutathione S-transferase (GST), positions two UBAs for higher affinity, avid interactions with Lys63-polyUb, but not with Lys48-polyUb. Freed from GST, these UBAs are either nonselective or prefer Lys48-polyUb. Accordingly, NMR experiments reveal no Lys63-polyUb-specific binding epitopes for these UBAs. We reexamine previous conclusions based on GST-UBAs and present an alternative model for how UBAs achieve a diverse range of linkage specificities.
- Publication
Nature structural & molecular biology, 2009, Vol 16, Issue 8, p883
- ISSN
1545-9985
- Publication type
Journal Article
- DOI
10.1038/nsmb.1637