Structure of ubiquitin-fold modifier 1-specific protease UfSP2

J Biol Chem. 2011 Mar 25;286(12):10248-57. doi: 10.1074/jbc.M110.172171. Epub 2011 Jan 12.

Abstract

Ubiquitin-fold modifier 1 (Ufm1)-specific protease 2 (UfSP2) is a cysteine protease that is responsible for the release of Ufm1 from Ufm1-conjugated cellular proteins, as well as for the generation of mature Ufm1 from its precursor. The 2.6 Å resolution crystal structure of mouse UfSP2 reveals that it is composed of two domains. The C-terminal catalytic domain is similar to UfSP1 with Cys(294), Asp(418), His(420), Tyr(282), and a regulatory loop participating in catalysis. The novel N-terminal domain shows a unique structure and plays a role in the recognition of its cellular substrate C20orf116 and thus in the recruitment of UfSP2 to the endoplasmic reticulum, where C20orf116 predominantly localizes. Mutagenesis studies were carried out to provide the structural basis for understanding the loss of catalytic activity observed in a recently identified UfSP2 mutation that is associated with an autosomal dominant form of hip dysplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalysis
  • Crystallography, X-Ray
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / genetics
  • Hip Dislocation, Congenital / enzymology
  • Hip Dislocation, Congenital / genetics
  • Humans
  • Mice
  • Protein Structure, Tertiary
  • Proteins*

Substances

  • Proteins
  • Ufm1 protein, mouse
  • Cysteine Endopeptidases
  • UfSP2 protein, mouse

Associated data

  • PDB/3OQC