Cryo-EM structures of apo-APC/C and APC/C<sup>CDH1:EMI1</sup> complexes provide insights into APC/C regulation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39567505.
- Also identified by DOI 10.1038/s41467-024-54398-5 and PMC identifier 11579458.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
APC/C is a multi-subunit complex that functions as a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle regulatory proteins for degradation. The APC/C itself is regulated by the sequential action of its coactivator subunits CDC20 and CDH1, post-translational modifications, and its inhibitory binding partners EMI1 and the mitotic checkpoint complex. In this study, we took advantage of developments in cryo-electron microscopy to determine the structures of human APC/C<sup>CDH1:EMI1</sup> and apo-APC/C at 2.9 Å and 3.2 Å resolution, respectively, providing insights into the regulation of APC/C activity. The high-resolution maps allow the unambiguous assignment of an α-helix to the N-terminus of CDH1 (CDH1<sup>α1</sup>) in the APC/C<sup>CDH1:EMI1</sup> ternary complex. We also identify a zinc-binding module in APC2 that confers structural stability to the complex, and we confirm the presence of zinc ions experimentally. Finally, due to the higher resolution and well defined density of these maps, we are able to build, aided by AlphaFold predictions, several intrinsically disordered regions in different APC/C subunits that likely play a role in proper APC/C assembly and regulation of its activity.
Medical subject headings
- Cryoelectron Microscopy
- Anaphase-Promoting Complex-Cyclosome