PDBsum entry 5l9u

Signaling protein

PDB id: 5l9u

Contents

Protein chains

1342 a.a.*

71 a.a.*

474 a.a.*

55 a.a.*

56 a.a.*

482 a.a.*

25 a.a.*

719 a.a.*

499 a.a.*

176 a.a.*

49 a.a.*

610 a.a.*

676 a.a.*

425 a.a.*

385 a.a.*

86 a.a.*

145 a.a.*

380 a.a.*

399 a.a.*

* C-alpha coords only

References listed in PDB file

Key reference

• Title: Dual ring e3 architectures regulate multiubiquitination and ubiquitin chain elongation by apc/c.
• Authors: N.G.Brown, R.Vanderlinden, E.R.Watson, F.Weissmann, A.Ordureau, K.P.Wu, W.Zhang, S.Yu, P.Y.Mercredi, J.S.Harrison, I.F.Davidson, R.Qiao, Y.Lu, P.Dube, M.R.Brunner, C.R.Grace, D.J.Miller, D.Haselbach, M.A.Jarvis, M.Yamaguchi, D.Yanishevski, G.Petzold, S.S.Sidhu, B.Kuhlman, M.W.Kirschner, J.W.Harper, J.M.Peters, H.Stark, B.A.Schulman.
• Ref.: Cell, 2016, 165, 1440-1453. [DOI no: 10.1016/j.cell.2016.05.037]
• PubMed id: 27259151

Abstract

Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination.