RGD Reference Report - Mechanism of ubiquitylation by dimeric RING ligase RNF4. - Rat Genome Database

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Mechanism of ubiquitylation by dimeric RING ligase RNF4.

Authors: Plechanovova, A  Jaffray, EG  McMahon, SA  Johnson, KA  Navratilova, I  Naismith, JH  Hay, RT 
Citation: Plechanovova A, etal., Nat Struct Mol Biol. 2011 Aug 21;18(9):1052-9. doi: 10.1038/nsmb.2108.
RGD ID: 9831417
Pubmed: PMID:21857666   (View Abstract at PubMed)
PMCID: PMC3326525   (View Article at PubMed Central)
DOI: DOI:10.1038/nsmb.2108   (Journal Full-text)

Mammalian RNF4 is a dimeric RING ubiquitin E3 ligase that ubiquitylates poly-SUMOylated proteins. We found that RNF4 bound ubiquitin-charged UbcH5a tightly but free UbcH5a weakly. To provide insight into the mechanism of RING-mediated ubiquitylation, we docked the UbcH5~ubiquitin thioester onto the RNF4 RING structure. This revealed that with E2 bound to one monomer of RNF4, the thioester-linked ubiquitin could reach across the dimer to engage the other monomer. In this model, the 'Ile44 hydrophobic patch' of ubiquitin is predicted to engage a conserved tyrosine located at the dimer interface of the RING, and mutation of these residues blocked ubiquitylation activity. Thus, dimeric RING ligases are not simply inert scaffolds that bring substrate and E2-loaded ubiquitin into close proximity. Instead, they facilitate ubiquitin transfer by preferentially binding the E2~ubiquitin thioester across the dimer and activating the thioester bond for catalysis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein autoubiquitination  IDA 9831417 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Rnf4  (ring finger protein 4)


Additional Information