The structure of SENP1-SUMO-2 complex suggests a structural basis for discrimination between SUMO paralogues during processing

Lin Nan Shen, Changjiang Dong, Huanting Liu, James H Naismith, Ronald T Hay

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The SUMO (small ubiquitin-like modifier)-specific protease SENP1 (sentrin-specific protease 1) can process the three forms of SUMO to their mature forms and deconjugate SUMO from modified substrates. It has been demonstrated previously that SENP1 processed SUMO-1 more efficiently than SUMO-2, but displayed little difference in its ability to deconjugate the different SUMO paralogues from modified substrates. To determine the basis for this substrate specificity, we have determined the crystal structure of SENP1 in isolation and in a transition-state complex with SUMO-2. The interface between SUMO-2 and SENP1 has a relatively poor complementarity, and most of the recognition is determined by interaction between the conserved C-terminus of SUMO-2 and the cleft in the protease. Although SENP1 is rather similar in structure to the related protease SENP2, these proteases have different SUMO-processing activities. Electrostatic analysis of SENP1 in the region where the C-terminal peptide, removed during maturation, would project indicates that it is the electrostatic complementarity between this region of SENP1 and the C-terminal peptides of the various SUMO paralogues that mediates selectivity.
Original languageEnglish
Pages (from-to)279-88
Number of pages10
JournalBiochemical Journal
Volume397
Issue number2
DOIs
Publication statusPublished - 15 Jul 2006

Keywords

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Endopeptidases
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Small Ubiquitin-Related Modifier Proteins
  • Static Electricity
  • Substrate Specificity

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