Insights into Anaphase Promoting Complex TPR subdomain assembly from a CDC26–APC6 structure

Departments of Structural Biology and Genetics/Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nature Structural & Molecular Biology (Impact Factor: 13.31). 09/2009; 16(9):987-9. DOI: 10.1038/nsmb.1645
Source: PubMed


The multisubunit anaphase promoting complex (APC) is an essential cell-cycle regulator. Although CDC26 is known to have a role in APC assembly, its molecular function has remained unclear. Biophysical, structural and genetic studies presented here reveal that CDC26 stabilizes the structure of APC6, a core TPR protein required for APC integrity. Notably, CDC26-APC6 association involves an intermolecular TPR mimic composed of one helix from each protein.

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    • "The TPR superhelices of Apc5 and Apc6 are also similar (DALI score of 16) (Table 1 and Supplementary Fig. 5b). The N-terminus of the TPR superhelix is stabilized by the extended N-terminus of the TPR-accessory subunit Apc15 that lines the internal groove of the TPR superhelix (Fig. 6a), reminiscent of Apc12 interactions with the C-terminal superhelical turn of Apc6 [33] [35]. The C-terminal 13 residues of Apc5 fold back into the TPR superhelix, and this segment of Apc5, together with the N-terminus of Apc15, encloses a cavity within the C-terminus of Apc5 TPR . "
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    • "Pull-downs confirm this notion , as GST-tagged IFT52 281–329 but not IFT52 330–381 interacts with IFT88 (Fig. 3 A). The reciprocal mapping of the IFT52-interacting IFT70 including importin  (Conti et al., 1998), the O-linked GlcNAc sugar transferase (Jínek et al., 2004), and the anaphase promoting complex subunit APC6 (Wang et al., 2009a). "
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    • "LOC641788 encodes a protein similar to the CDC26 subunit of the anaphase promoting complex (APC), an essential cell-cycle regulator. [43] It regulates by promoting ubiquitin-mediated proteolysis of key cell cycle regulatory proteins. Finally, STAT 4 is a signal transducer and activator of transcription. "
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