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

25 Citations (Scopus)


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
Issue number1
Publication statusPublished - Jul 15 2014


  • 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

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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