Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast

Mol Cell. 2000 May;5(5):865-76. doi: 10.1016/s1097-2765(00)80326-3.

Abstract

Modification of cellular proteins by the ubiquitin-like protein SUMO is essential for nuclear processes and cell cycle progression in yeast. The Ulp1 protease catalyzes two essential functions in the SUMO pathway: (1) processing of full-length SUMO to its mature form and (2) deconjugation of SUMO from targeted proteins. Selective reduction of the proteolytic reaction produced a covalent thiohemiacetal transition state complex between a Ulp1 C-terminal fragment and its cellular substrate Smt3, the yeast SUMO homolog. The Ulp1-Smt3 crystal structure and functional testing of elements within the conserved interface elucidate determinants of SUMO recognition, processing, and deconjugation. Genetic analysis guided by the structure further reveals a regulatory element N-terminal to the proteolytic domain that is required for cell growth in yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism
  • Fungal Proteins / chemistry*
  • Glycine
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Saccharomyces cerevisiae
  • Sequence Homology, Amino Acid
  • Small Ubiquitin-Related Modifier Proteins*
  • Substrate Specificity
  • Surface Properties
  • Ubiquitins / chemistry*

Substances

  • Fungal Proteins
  • Peptide Fragments
  • SUMO2 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitins
  • Cysteine Endopeptidases
  • Ulp1 protease
  • Glycine

Associated data

  • PDB/1EUV