The RanBP2 SUMO E3 ligase is neither HECT- nor RING-type

Nat Struct Mol Biol. 2004 Oct;11(10):984-91. doi: 10.1038/nsmb834. Epub 2004 Sep 19.

Abstract

Post-translational modification with the ubiquitin-related protein SUMO1 requires the E1 enzyme Aos1-Uba2 and the E2 enzyme Ubc9. Distinct E3 ligases strongly enhance modification of specific targets. The SUMO E3 ligase RanBP2 (also known as Nup358) has no obvious similarity to RING- or HECT-type enzymes. Here we show that RanBP2's 30-kDa catalytic fragment is a largely unstructured protein. Despite two distinct but partially overlapping 79-residue catalytic domains, one of which is sufficient for maximal activity, RanBP2 binds to Ubc9 in a 1:1 stoichiometry. The identification of nine RanBP2 and three Ubc9 side chains that are important for RanBP2-dependent SUMOylation indicates largely hydrophobic interactions. These properties distinguish RanBP2 from all other known E3 ligases, and we speculate that RanBP2 exerts its catalytic effect by altering Ubc9's properties rather than by mediating target interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Molecular Chaperones
  • Molecular Sequence Data
  • Nuclear Pore Complex Proteins / chemistry
  • Nuclear Pore Complex Proteins / metabolism
  • Nuclear Pore Complex Proteins / physiology*
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Substrate Specificity

Substances

  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • ran-binding protein 2