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

@article{Pichler2004TheRS,
  title={The RanBP2 SUMO E3 ligase is neither HECT- nor RING-type},
  author={Andrea Pichler and Puck Knipscheer and Hisato Saitoh and Titia K. Sixma and Frauke Melchior},
  journal={Nature Structural \&Molecular Biology},
  year={2004},
  volume={11},
  pages={984-991}
}
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… 
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TLDR
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Structural insights, combined with biochemical and kinetic data obtained with additional substrates, support a model in which Nup358/RanBP2 acts as an E3 by binding both SUMO and Ubc9 to position the SUMO–E2-thioester in an optimal orientation to enhance conjugation.
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Canonical ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates…
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    Nature Structural &Molecular Biology
  • 2006
TLDR
It seems that Ubc9 uses an indirect mechanism to activate lysine for conjugation that may be conserved among E2 family members.
Protein-protein interactions regulate Ubl conjugation.
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TLDR
The data suggest that elements in both IR1 and IR2 exhibit specificity for SUMO1, and deletions and domain swap constructs in protease protection assays and automodification assays suggest that differences in SUMO specificity may be achieved through these subtle conformational differences.
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