GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:21857666

From GONUTS
Jump to: navigation, search
Citation

Plechanovová, A, Jaffray, EG, McMahon, SA, Johnson, KA, Navrátilová, I, Naismith, JH and Hay, RT (2011) Mechanism of ubiquitylation by dimeric RING ligase RNF4. Nat. Struct. Mol. Biol. 18:1052-9

Abstract

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.

Links

PubMed PMC3326525 Online version:10.1038/nsmb.2108

Keywords

Animals; Binding, Competitive; Catalytic Domain; Dimerization; Models, Molecular; Nuclear Proteins/chemistry; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Protein Structure, Tertiary; RING Finger Domains; Rats; Recombinant Fusion Proteins/chemistry; Transcription Factors/chemistry; Transcription Factors/metabolism; Transcription Factors/physiology; Ubiquitin-Conjugating Enzymes/metabolism; Ubiquitination

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:RNF4

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:3583

F

Seeded From UniProt

complete

RAT:RNF4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P51668

F

Seeded From UniProt

complete

HUMAN:UB2D1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O88846

F

Seeded From UniProt

complete

RAT:RNF4

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O88846

F

Seeded From UniProt

complete

RAT:RNF4

enables

GO:0008270: zinc ion binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:RNF4

enables

GO:0031624: ubiquitin conjugating enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:1317341

F

Seeded From UniProt

complete

RAT:RNF4

enables

GO:0042803: protein homodimerization activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:RNF4

involved_in

GO:0051865: protein autoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:RNF4

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.