6TNT

SUMOylated apoAPC/C with repositioned APC2 WHB domain

Summary for 6TNT

• Entry DOI: 10.2210/pdb6tnt/pdb
• EMDB information: 10536
• Descriptor: Anaphase-promoting complex subunit 1, Anaphase-promoting complex subunit 10, Anaphase-promoting complex subunit 13, ... (16 entities in total)
• Functional Keywords: apc/c, apc2, whb domain, sumoylation, cell cycle
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 20
• Total formula weight: 1173802.88

Authors

Barford, D.,Yatskevich, S. (deposition date: 2019-12-10, release date: 2021-01-13, Last modification date: 2024-11-13)

Primary citation

Yatskevich, S.,Kroonen, J.S.,Alfieri, C.,Tischer, T.,Howes, A.C.,Clijsters, L.,Yang, J.,Zhang, Z.,Yan, K.,Vertegaal, A.C.O.,Barford, D.
Molecular mechanisms of APC/C release from spindle assembly checkpoint inhibition by APC/C SUMOylation.
Cell Rep, 34:108929-108929, 2021

PubMed Abstract: The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the attachment of sister chromatids to the mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation. To understand the structural and functional consequences of APC/C SUMOylation, we reconstituted SUMOylated APC/C for electron cryo-microscopy and biochemical analyses. SUMOylation of the APC/C causes a substantial rearrangement of the WHB domain of APC/C's cullin subunit (APC2). Although APC/C SUMOylation results in a modest impact on normal APC/C activity, repositioning APC2 reduces the affinity of APC/C for the mitotic checkpoint complex (MCC), the effector of the SAC. This attenuates MCC-mediated suppression of APC/C activity, allowing for more efficient ubiquitination of APC/C substrates in the presence of the MCC. Thus, SUMOylation stimulates the reactivation of APC/C when the SAC is silenced, contributing to timely anaphase onset.

PubMed: 33789095
DOI: 10.1016/j.celrep.2021.108929

Experimental method

ELECTRON MICROSCOPY (3.78 Å)