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… 
Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a mechanism for SUMO paralog selection
TLDR
It is shown that E2-E3 interactions are not conserved across the ubiquitin-like protein superfamily and a RanBP2-dependent mechanism for SUMO paralog–specific conjugation is identified.
Reconstitution of the Recombinant RanBP2 SUMO E3 Ligase Complex.
TLDR
A detailed protocol to in vitro reconstitute the RanBP2 SUMO E3 ligase complex and presents details for the assembly and final purification of the catalytically active Ran BP2/RanGAP1*SUMO1/Ubc9 complex.
Ubc9 sumoylation regulates SUMO target discrimination.
The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase.
Structural basis for catalytic activation by the human ZNF451 SUMO E3 ligase
E3 protein ligases enhance transfer of ubiquitin-like (Ubl) proteins from E2 conjugating enzymes to substrates by stabilizing the thioester-charged E2~Ubl in a closed configuration optimally aligned
Insights into E3 ligase activity revealed by a SUMO–RanGAP1–Ubc9–Nup358 complex
TLDR
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.
Crystal Structure of UBA2ufd-Ubc9: Insights into E1-E2 Interactions in Sumo Pathways
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
Lysine activation and functional analysis of E2-mediated conjugation in the SUMO pathway
  • A. Yunus, C. Lima
  • Chemistry, Biology
    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.
Determinants of Small Ubiquitin-like Modifier 1 (SUMO1) Protein Specificity, E3 Ligase, and SUMO-RanGAP1 Binding Activities of Nucleoporin RanBP2*
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.
...
...

References

SHOWING 1-10 OF 40 REFERENCES
The APC11 RING-H2 finger mediates E2-dependent ubiquitination.
TLDR
Evidence is provided that the Saccharomyces cerevisiae RING-H2 finger protein Apc11 defines the minimal ubiquitin ligase activity of the anaphase-promoting complex or cyclosome, and it is suggested that Apc 11p is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiqu itin to APC substrates in vivo.
The APC 11 RING-H 2 Finger Mediates E 2-Dependent Ubiquitination
TLDR
Evidence is provided that the Saccharomyces cerevisiae RING-H2 finger protein Apc11 defines the minimal ubiquitin ligase activity of the anaphase-promoting complex or cyclosome, and it is suggested that Apc 11p is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitIn to APC substrates in vivo.
Perturbation of SUMOlation Enzyme Ubc9 by Distinct Domain within Nucleoporin RanBP2/Nup358*
TLDR
It is emphasized that the IR1+2 domain is a useful tool for manipulating the nuclear localization of Ubc9 and perturbing the subcellular localization of SUMOs and/or SUMOlated proteins, and the important role of nuclear Ubc 9 in the Rad51-mediated homologous recombination pathway, possibly by modulating intracellular trafficking of Rad51 is emphasized.
Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity
  • D. Schmidt, S. Müller
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
TLDR
This work shows that two members of the PIAS family, PIAS1 and PIASxβ, act as specific E3-like ligases that promote sumoylation of p53 and c-Jun in vitro and in vivo, and extends the analogy between the ubiquitin and SUMO pathway.
Versatile protein tag, SUMO: Its enzymology and biological function
TLDR
SUMO modification of target proteins is involved in nuclear protein targeting, formation of subnuclear structures, regulation of transcriptional activities or DNA binding abilities of transcription factors, and control of protein stability.
U-box proteins as a new family of ubiquitin ligases.
...
...