5LGG

The N-terminal WD40 domain of Apc1 (Anaphase promoting complex subunit 1)

Summary for 5LGG

• Entry DOI: 10.2210/pdb5lgg/pdb
• Descriptor: Anaphase-promoting complex subunit 1,Anaphase-promoting complex subunit 1,Anaphase-promoting complex subunit 1,Anaphase-promoting complex subunit 1 (2 entities in total)
• Functional Keywords: apc/c, cell cycle, wd40
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 47909.46

Authors

Li, Q.,Aibara, S.,Barford, D. (deposition date: 2016-07-07, release date: 2016-10-05, Last modification date: 2024-01-10)

Primary citation

Li, Q.,Chang, L.,Aibara, S.,Yang, J.,Zhang, Z.,Barford, D.
WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity.
Proc.Natl.Acad.Sci.USA, 113:10547-10552, 2016

PubMed Abstract: The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C.

PubMed: 27601667
DOI: 10.1073/pnas.1607147113

Experimental method

X-RAY DIFFRACTION (2.15 Å)