Structural Insight into Ubiquitin-Like Protein Recognition and Oligomeric States of JAMM/MPN + Proteases

Structure. 2017 Jun 6;25(6):823-833.e6. doi: 10.1016/j.str.2017.04.002. Epub 2017 May 4.

Abstract

JAMM/MPN+ metalloproteases cleave (iso)peptide bonds C-terminal to ubiquitin (Ub) and ubiquitin-like protein (Ubl) domains and typically require association with protein partners for activity, which has limited a molecular understanding of enzyme function. To provide an insight, we solved the X-ray crystal structures of a catalytically active Pyrococcus furiosus JAMM/MPN+ metalloprotease (PfJAMM1) alone and in complex with a Ubl (PfSAMP2) to 1.7- to 1.9-Å resolution. PfJAMM1 was found to have a redox sensitive dimer interface. In the PfJAMM1-bound state of the SAMP2, a Ubl-to-Ub conformational change was detected. Surprisingly, distant homologs of PfJAMM1 were found to be closely related in 3D structure, including the interface for Ubl/Ub binding. From this work, we infer the molecular basis of how JAMM/MPN+ proteases recognize and cleave Ubl/Ub tags from diverse proteins and highlight an α2-helix structural element that is conserved and crucial for binding and removing the Ubl SAMP2 tag.

Keywords: archaea; deubiquitinase; metalloprotease; ubiquitin; ubiquitin-like protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Metalloproteases / chemistry*
  • Metalloproteases / metabolism*
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Conformation
  • Protein Domains
  • Protein Multimerization
  • Pyrococcus furiosus / enzymology*
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism

Substances

  • Archaeal Proteins
  • Multiprotein Complexes
  • Ubiquitin
  • Metalloproteases