Tetrameric Assembly of Monoubiquitin Accurately Mimics the Lys11 Polyubiquitin Chain Structure

Biochemistry. 2015 Aug 4;54(30):4704-10. doi: 10.1021/acs.biochem.5b00498. Epub 2015 Jul 22.

Abstract

Specific lysine residues on the ubiquitin surface were selected during the course of evolution to form different polyubiquitin chain structures that signal diverse cellular processes. A vast number of ubiquitin receptors specifically recognize and decode the signals conferred by these polyubiquitin chains. The mechanisms of formation and the structure of Lys11-linked ubiquitin, which signals for cell-cycle and innate immune control, have been elucidated. Here, we present a new crystal structure of monomeric ubiquitin that accurately mimics one of the structures of Lys11-linked ubiquitin. Analysis of the ubiquitin:ubiquitin interface demonstrates structural fitness and specificity. The interaction is exclusively hydrophilic, leaving the Ile44 hydrophobic patch, a major recognition site for ubiquitin receptors, exposed. These noncovalent ubiquitin:ubiquitin interactions are nearly identical to those reported for Lys11-linked ubiquitin and seem to play a significant role in stabilizing the crystal structure without the isopeptide bond. In vitro cross-linking analysis with wild-type ubiquitin or its mutants partially mimics the interactions in the crystal. We suggest that these interactions may play a biological role in transmitting Lys11-linked ubiquitin chain-type cellular signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Humans
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Mutation, Missense
  • Protein Multimerization*
  • Signal Transduction
  • Structure-Activity Relationship
  • Ubiquitin / chemistry*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism

Substances

  • Multiprotein Complexes
  • Ubiquitin

Associated data

  • PDB/4Z9S