Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a mechanism for SUMO paralog selection

M H Tatham, S Kim, E Jaffray, J Song, Y Chen, R T Hay

Research output: Contribution to journalArticlepeer-review

108 Citations (Scopus)

Abstract

The conjugation of small ubiquitin-like modifiers SUMO-1, SUMO-2 and SUMO-3 onto target proteins requires the concerted action of the specific E1-activating enzyme SAE1/SAE2, the E2-conjugating enzyme Ubc9, and an E3-like SUMO ligase. NMR chemical shift perturbation was used to identify the surface of Ubc9 that interacts with the SUMO ligase RanBP2. Unlike known ubiquitin E2-E3 interactions, RanBP2 binds to the beta-sheet of Ubc9. Mutational disruption of Ubc9-RanBP2 binding affected SUMO-2 but not SUMO-1 conjugation to Sp100 and to a newly identified RanBP2 substrate, PML. RanBP2 contains a binding site specific for SUMO-1 but not SUMO-2, indicating that a Ubc9-SUMO-1 thioester could be recruited to RanBP2 via SUMO-1 in the absence of strong binding between Ubc9 and RanBP2. Thus we show that E2-E3 interactions are not conserved across the ubiquitin-like protein superfamily and identify a RanBP2-dependent mechanism for SUMO paralog-specific conjugation.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalNature Structural and Molecular Biology
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 2005

Keywords

  • E3 LIGASE
  • UBIQUITIN LIGASE
  • YEAST SEPTINS/
  • CONJUGATION
  • PROTEIN
  • DOMAIN
  • NUCLEAR
  • SYSTEM
  • IDENTIFICATION
  • TRANSCRIPTION

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