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


Kung Camy C.-H.123,Naik Mandar T.1,Wang Szu-Huan4,Shih Hsiu-Ming1,Chang Che-Chang5,Lin Li-Ying6,Chen Chia-Lin26,Ma Che6,Chang Chi-Fon6,Huang Tai-Huang167


1. Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan

2. Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan

3. Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan

4. Scientific Instrument Center, Academia Sinica, Taipei 11529, Taiwan

5. Graduate Institute of Translational Medicine, Taipei Medical University, Taipei 110, Taiwan

6. Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan

7. Department of Physics, National Taiwan Normal University, Taipei 11677, Taiwan


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 domain was 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.


Portland Press Ltd.


Cell Biology,Molecular Biology,Biochemistry







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