Molecular architecture and mechanism of the anaphase-promoting complex

Chang, Leifu; Zhang, Ziguo; Yang, Jing; McLaughlin, Stephen H.; Barford, David

doi:10.1038/nature13543

Cited by 189 publications

(383 citation statements)

References 68 publications

(112 reference statements)

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“…A study using TAP-MS in Arabidopsis cell suspension cultured cells identified at least 11 APC subunits (Capron et al 2003;Van Leene et al 2010). Three dimensional reconstruction of human APC has shown that the complex adopts a triangular shape, a bit similar-looking as an open shell (Chang et al 2014). The backbone contains a lobe of tetratricopeptide (TPR) domain-containing subunits APC3, APC6, APC7 and APC8, and a platform built out of APC1, APC4 and APC5.…”

Section: Apcmentioning

confidence: 99%

Transferring an optimized TAP-toolbox for the isolation of protein complexes to a portfolio of rice tissues

et al. 2016

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Proteins are the cell's functional entities. Rather than operating independently, they interact with other proteins. Capturing in vivo protein complexes is therefore crucial to gain understanding of the function of a protein in a cellular context. Affinity purification coupled to mass spectrometry has proven to yield a wealth of information about protein complex constitutions for a broad range of organisms. For Oryza sativa, the technique has been initiated in callus and shoots, but has not been optimized ever since. We translated an optimized tandem affinity purification (TAP) approach from Arabidopsis thaliana toward Oryza sativa, and demonstrate its applicability in a variety of rice tissues. A list of non-specific and false positive interactors is presented, based on reoccurrence over more than 170 independent experiments, to filter bona fide interactors. We demonstrate the sensitivity of our approach by isolating the complexes for the rice ANAPHASE PROMOTING COMPLEX SUB-UNIT 10 (APC10) and CYCLIN-DEPENDENT KINASE D (CDKD) proteins from the proliferation zone of the emerging fourth leaf. Next to APC10 and CDKD, we tested several additional baits in the different rice tissues and reproducibly retrieved at least one interactor for 81.4 % of the baits screened for in callus tissue and T1 seedlings. By transferring an optimized TAP tag combined with state-ofthe-art mass spectrometry, our TAP protocol enables the discovery of interactors for low abundance proteins in rice and opens the possibility to capture complex dynamics by comparing tissues at different stages of a developing rice organ.

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Section: Apcmentioning

confidence: 99%

Transferring an optimized TAP-toolbox for the isolation of protein complexes to a portfolio of rice tissues

et al. 2016

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“…Previous cryo-EM studies showed that Cdh1 association with the APC/C promotes substantial conformational changes in the catalytic module and the neighboring platform subunits Apc1, Apc4, and Apc5 (12). This change in conformation exposes the UbcH10-binding site of the catalytic module, enhancing UbcH10 association and thereby stimulating APC/C E3 ligase activity (12,19).…”

Section: Significancementioning

confidence: 99%

“…APC/C activity is controlled by its association with one of two coactivator subunits (either Cdc20 or Cdh1) that function to specify substrate recognition and stimulate ubiquitin transfer reactions (11)(12)(13)(14). The mitotic coactivator Cdc20 preferentially binds to hyperphosphorylated APC/C, whereas Cdh1 also binds to unphosphorylated APC/C.…”

mentioning

confidence: 99%

“…Coactivators enhance vertebrate APC/C catalytic activity by increasing its affinity for the priming E2 UbcH10 (also known as "Ube2C") (12), whereas in budding yeast APC/C coactivators enhance E2 catalytic efficiency (13). The APC/C is a multisubunit E3 ligase composed of 15 different proteins (12). Five are tetratricopeptide repeat (TPR) proteins, four of which (Apc3, Apc6, Apc7, and Apc8) form structurally related homodimers.…”

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confidence: 99%

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WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity

Chang

Aibara

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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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 (Apc1WD40). To understand how Apc1WD40 contributes to APC/C activity, a mutant form of the APC/C with Apc1WD40 deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1WD40 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 Apc1WD40 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 Apc1WD40 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.

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“…Cdc20 is replaced by Cdh1 later in mitosis in somatic cell cycles. Cdc20 and Cdh1 bind reversibly to the APC/C and, in doing so, activate it by changing its conformation to reposition APC11 to recruit the E2 enzyme in closer proximity to the bound substrate (Chang et al 2014). Cdc20 and Cdh1 are WD40 family members and the aminoterminal residues of the D-box bind between blades 1 and 7 of the WD40 domain; the carboxy-terminal residues bind to APC10 (He et al 2013).…”

Section: Sister Chromatid Separationmentioning

confidence: 99%

The Biochemistry of Mitosis

Wieser

Pines

2015

Cold Spring Harb Perspect Biol

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In this article, we will discuss the biochemistry of mitosis in eukaryotic cells. We will focus on conserved principles that, importantly, are adapted to the biology of the organism. It is vital to bear in mind that the structural requirements for division in a rapidly dividing syncytial Drosophila embryo, for example, are markedly different from those in a unicellular yeast cell. Nevertheless, division in both systems is driven by conserved modules of antagonistic protein kinases and phosphatases, underpinned by ubiquitin-mediated proteolysis, which create molecular switches to drive each stage of division forward. These conserved control modules combine with the self-organizing properties of the subcellular architecture to meet the specific needs of the cell. Our discussion will draw on discoveries in several model systems that have been important in the long history of research on mitosis, and we will try to point out those principles that appear to apply to all cells, compared with those in which the biochemistry has been specifically adapted in a particular organism.

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Molecular architecture and mechanism of the anaphase-promoting complex

Cited by 189 publications

References 68 publications

Transferring an optimized TAP-toolbox for the isolation of protein complexes to a portfolio of rice tissues

Transferring an optimized TAP-toolbox for the isolation of protein complexes to a portfolio of rice tissues

WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity

The Biochemistry of Mitosis

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