Structural analysis of poly-SUMO chain recognition by the RNF4-SIMs domain

Camy C.H. Kung, Mandar T. Naik, Szu Huan Wang, Hsiu Ming Shih, Che Chang Chang, Li Ying Lin, Chia Lin Chen, Che Ma, Chi Fon Chang, Tai Huang Huang

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The E3 ubiquitin ligase RNF4 (RING finger protein 4) contains four tandem SIM [SUMO (small ubiquitin-like modifier)-interaction motif] repeats for selective interaction with poly-SUMO-modified proteins, which it targets for degradation. We employed a multi-faceted approach to characterize the structure of the RNF4-SIMs domain and the tetra-SUMO2 chain to elucidate the interaction between them. In solution, the SIM domainwas intrinsically disordered and the linkers of the tetra-SUMO2 were highly flexible. Individual SIMs of the RNF4-SIMs domains bind to SUMO2 in the groove between the β2-strand and the α1-helix parallel to the β2-strand. SIM2 and SIM3 bound to SUMO with a high affinity and together constituted the recognition module necessary for SUMO binding. SIM4 alone bound to SUMO with low affinity; however, its contribution to tetra-SUMO2 binding avidity is comparable with that of SIM3 when in the RNF4-SIMs domain. The SAXS data of the tetra-SUMO2-RNF4-SIMs domain complex indicate that it exists as an ordered structure. The HADDOCK model showed that the tandem RNF4-SIMs domain bound antiparallel to the tetra-SUMO2 chain orientation and wrapped around the SUMO protamers in a superhelical turn without imposing steric hindrance on either molecule.

Original languageEnglish
Pages (from-to)53-65
Number of pages13
JournalBiochemical Journal
Volume462
Issue number1
DOIs
Publication statusPublished - 2014 Jul 15

Keywords

  • Nuclear magnetic resonance (NMR)
  • RING finger 4 (RNF4)
  • SUMO-interactionmotif (SIM)
  • Small ubiquitin-likemodifier (SUMO)
  • Small-angle X-ray scattering (SAXS)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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