A Ubiquitin-Binding Domain that Binds a Structural Fold Distinct from that of Ubiquitin

Structure. 2019 Aug 6;27(8):1316-1325.e6. doi: 10.1016/j.str.2019.05.003. Epub 2019 Jun 13.

Abstract

Ubiquitylation, the posttranslational linkage of ubiquitin moieties to lysines in target proteins, helps regulate a myriad of biological processes. Ubiquitin, and sometimes ubiquitin-homology domains, are recognized by ubiquitin-binding domains, including CUE domains. CUE domains are thus generally thought to function by mediating interactions with ubiquitylated proteins. The chromatin remodeler, SMARCAD1, interacts with KAP1, a transcriptional corepressor. The SMARCAD1-KAP1 interaction is direct and involves the first SMARCAD1 CUE domain (CUE1) and the RBCC domain of KAP1. Here, we present a structural model of the KAP1 RBCC-SMARCAD1 CUE1 complex based on X-ray crystallography. Remarkably, CUE1, a canonical CUE domain, recognizes a cluster of exposed hydrophobic and surrounding charged/amphipathic residues on KAP1, which are presented in the context of a coiled-coil domain, not in a structure resembling ubiquitin. Together, these data suggest that CUE domains may have a wider function than simply recognizing ubiquitin and the ubiquitin-fold.

Keywords: CUE domain; KAP1; SMARCAD1; TIF1β; TRIM28; UBA domain; ubiquitin; ubiquitin-binding domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism*
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Domains
  • Tripartite Motif-Containing Protein 28 / chemistry*
  • Tripartite Motif-Containing Protein 28 / metabolism*
  • Ubiquitin / metabolism

Substances

  • Ubiquitin
  • TRIM28 protein, human
  • Tripartite Motif-Containing Protein 28
  • SMARCAD1 protein, human
  • DNA Helicases