4V3L

RNF38-UB-UbcH5B-Ub complex

Summary for 4V3L

• Entry DOI: 10.2210/pdb4v3l/pdb
• Related: 4V3K
• Descriptor: UBIQUITIN-CONJUGATING ENZYME E2 D2, POLYUBIQUITIN-C, E3 UBIQUITIN-PROTEIN LIGASE RNF38, ... (6 entities in total)
• Functional Keywords: ligase, ubiquitin, ring e3, e2
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 43884.63

Authors

Buetow, L.,Gabrielsen, M.,Anthony, N.G.,Dou, H.,Patel, A.,Aitkenhead, H.,Sibbet, G.J.,Smith, B.O.,Huang, D.T. (deposition date: 2014-10-20, release date: 2015-04-08, Last modification date: 2024-05-08)

Primary citation

Buetow, L.,Gabrielsen, M.,Anthony, N.G.,Dou, H.,Patel, A.,Aitkenhead, H.,Sibbet, G.J.,Smith, B.O.,Huang, D.T.
Activation of a Primed Ring E3-E2-Ubiquitin Complex by Non-Covalent Ubiquitin.
Mol.Cell, 58:297-, 2015

PubMed Abstract: RING ubiquitin ligases (E3) recruit ubiquitin-conjugate enzymes (E2) charged with ubiquitin (Ub) to catalyze ubiquitination. Non-covalent Ub binding to the backside of certain E2s promotes processive polyUb formation, but the mechanism remains elusive. Here, we show that backside bound Ub (Ub(B)) enhances both RING-independent and RING-dependent UbcH5B-catalyzed donor Ub (Ub(D)) transfer, but with a more prominent effect in RING-dependent transfer. Ub(B) enhances RING E3s' affinities for UbcH5B-Ub, and RING E3-UbcH5B-Ub complex improves Ub(B)'s affinity for UbcH5B. A comparison of the crystal structures of a RING E3, RNF38, bound to UbcH5B-Ub in the absence and presence of Ub(B), together with molecular dynamics simulation and biochemical analyses, suggests Ub(B) restricts the flexibility of UbcH5B's α1 and α1β1 loop. Ub(B) supports E3 function by stabilizing the RING E3-UbcH5B-Ub complex, thereby improving the catalytic efficiency of Ub transfer. Thus, Ub(B) serves as an allosteric activator of RING E3-mediated Ub transfer.

PubMed: 25801170
DOI: 10.1016/J.MOLCEL.2015.02.017

Experimental method

X-RAY DIFFRACTION (1.53 Å)