The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. (embl-heidelberg.de)
CDH15
The anaphase-promoting complex or cyclosome (APC) is an unusuallycomplicated ubiquitin ligase, composed of 13 core subunits and either oftwo loosely associated regulatory subunits, Cdc20 and Cdh1. (embl-heidelberg.de)
Apc4,Apc5, Cdc23, and Apc1 associate interdependently, such that loss of anyone subunit greatly reduces binding between the remaining three.Intriguingly, the cullin and TPR subunits both contribute to the bindingof Cdh1 to the APC. (embl-heidelberg.de)
Enzymatic assays performed with APC purified fromstrains lacking each of the essential subunits revealed that onlycdc27Delta complexes retain detectable activity in the presence of Cdh1.This residual activity depends on the C-box domain of Cdh1, but not on theC-terminal IR domain, suggesting that the C-box mediates a productiveinteraction with an APC subunit other than Cdc27. (embl-heidelberg.de)
The activator Cdc20 is then replaced by a second activator, Cdh1, and APC/C Cdh1 promotes complete degradation of M cyclin, followed by polo-like kinase 1, Aurora A, and other substrates, to complete mitosis and cytokinesis and drive progression into G1 [ 1 , 2 ]. (biomedcentral.com)
We analyzedthe architecture of the APC using a recently constructed budding yeaststrain that is viable in the absence of normally essential APC subunits.We found that the largest subunit, Apc1, serves as a scaffold thatassociates independently with two separable subcomplexes, one thatcontains Apc2 (Cullin), Apc11 (RING), and Doc1/Apc10, and another thatcontains the three TPR subunits (Cdc27, Cdc16, and Cdc23). (embl-heidelberg.de)
We found thatthe three TPR subunits display a sequential binding dependency, with Cdc27the most peripheral, Cdc23 the most internal, and Cdc16 between. (embl-heidelberg.de)
Three conserved tetratricopeptide repeat (TPR) subunits (Cdc16, Cdc23 and Cdc27) share related superhelical homo-dimeric architectures that assemble to generate a quasi-symmetrical structure. (ox.ac.uk)
Cyclin-depende2
These changes are orchestrated by a small number of master regulators, including the cyclin-dependent kinases (Cdks) and the anaphase-promoting complex/cyclosome (APC/C). Each Cdk or APC/C isoform has a large number of substrates, and the substrates of each isoform are modified in a specific order that leads to sequential substrate activation or inactivation. (biomedcentral.com)
Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apc1, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apc11 and Apc10 (also known as Doc1)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates. (ox.ac.uk)
One of the most complex ubiquitinligases is the anaphase-promoting complex (APC) - a 1.5-megadalton assemblage of 1-2 copies of each of 13 different subunits, as well as two diffusible activators. (nature.com)
The anaphase-promoting complex or cyclosome (APC/C) is an unusually large E3 ubiquitin ligase responsible for regulating defined cell cycle transitions. (ox.ac.uk)
The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
Tetratricopeptide1
This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction. (wikipedia.org)
Protein2
This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eucaryotic cells. (wikipedia.org)
Solving the structure of protein complexes is particularly challenging when they contain many subunits. (nature.com)
Microscopy1
The researchers report high-resolution structures of the APC that they obtained by electron microscopy (EM), generated from structures with different combinations of subunits, allowing them to infer the exact placement of many of its subunits. (nature.com)
It binds the Apc2 subunit, which is a part of the catalytic core, and interacts with coactivators Cdh1 or Cdc20 to recruit substrates to the complex. (nih.gov)
The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10," the authors write. (genomeweb.com)
Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. (genomeweb.com)
The catalytic activity of the APC/C and its ability to specify the destruction of particular proteins at different phases of the cell cycle are controlled by its interaction with two structurally related coactivator subunits, Cdc20 and Cdh1. (rcsb.org)
Researchers at the Institute of Cancer Research in the UK describe the structure of the mitotic checkpoint complex in Nature this week. (genomeweb.com)
Using the crystal structure of Schizosaccharomyces pombe 's mitotic checkpoint complex, the team shows the molecular basis of mitotic checkpoint complex-mediated anaphase-promoting complex/cyclosome inhibition. (genomeweb.com)
Recruitment1
Efficient phosphorylation of the auto-inhibitory segment, and thus relief of auto-inhibition, requires the recruitment of Cdk-cyclin in complex with a Cdk regulatory subunit (Cks) to a hyperphosphorylated loop of Apc3. (rcsb.org)
Specific1
Alkyl hydroperoxide reductase subunit C/ Thiol specific antioxidant [Interproscan]. (ntu.edu.sg)