5L9U

Model of human Anaphase-promoting complex/Cyclosome (APC/C-CDH1) with a cross linked Ubiquitin variant-substrate-UBE2C (UBCH10) complex representing key features of multiubiquitination

Summary for 5L9U

• Entry DOI: 10.2210/pdb5l9u/pdb
• EMDB information: 3432
• Descriptor: Anaphase-promoting complex subunit 1, Anaphase-promoting complex subunit 10, Anaphase-promoting complex subunit 13, ... (17 entities in total)
• Functional Keywords: ubiquitination, multi-protein complex, cell division, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 22
• Total formula weight: 1258625.00

Authors

Brown, N.G.,VanderLinden, R.,Dube, P.,Haselbach, D.,Peters, J.M.,Stark, H.,Schulman, B.A. (deposition date: 2016-06-11, release date: 2016-09-14, Last modification date: 2024-10-16)

Primary citation

Brown, N.G.,VanderLinden, R.,Watson, E.R.,Weissmann, F.,Ordureau, A.,Wu, K.P.,Zhang, W.,Yu, S.,Mercredi, P.Y.,Harrison, J.S.,Davidson, I.F.,Qiao, R.,Lu, Y.,Dube, P.,Brunner, M.R.,Grace, C.R.,Miller, D.J.,Haselbach, D.,Jarvis, M.A.,Yamaguchi, M.,Yanishevski, D.,Petzold, G.,Sidhu, S.S.,Kuhlman, B.,Kirschner, M.W.,Harper, J.W.,Peters, J.M.,Stark, H.,Schulman, B.A.
Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C.
Cell, 165:1440-1453, 2016

PubMed 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.

PubMed: 27259151
DOI: 10.1016/j.cell.2016.05.037

Experimental method

ELECTRON MICROSCOPY (6.4 Å)