2XEU

Ring domain

Summary for 2XEU

• Entry DOI: 10.2210/pdb2xeu/pdb
• Related PRD ID: PRD_900003
• Descriptor: RING FINGER PROTEIN 4, beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose, ZINC ION, ... (5 entities in total)
• Functional Keywords: transcription, zinc-finger, metal-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 7880.70

Authors

Plechanovova, A.,McMahon, S.A.,Johnson, K.A.,Navratilova, I.,Naismith, J.H.,Hay, R.T. (deposition date: 2010-05-18, release date: 2010-07-28, Last modification date: 2024-05-08)

Primary citation

Plechanovova, A.,Jaffray, E.G.,Mcmahon, S.A.,Johnson, K.A.,Navratilova, I.,Naismith, J.H.,Hay, R.T.
Mechanism of Ubiquitylation by Dimeric Ring Ligase Rnf4
Nat.Struct.Mol.Biol., 18:1052-, 2011

PubMed 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.

PubMed: 21857666
DOI: 10.1038/NSMB.2108

Experimental method

X-RAY DIFFRACTION (1.5 Å)