title: Understanding the structural basis for controlling chromosome division.
abstract: The process of chromosome division, termed mitosis, involves a complex sequence of events that is tightly controlled to ensure that the faithful segregation of duplicated chromosomes is coordinated with each cell division cycle. The large macromolecular complex responsible for regulating this process is the anaphase-promoting complex or cyclosome (APC/C). In humans, the APC/C is assembled from 20 subunits derived from 15 different proteins. The APC/C functions to ubiquitinate cell cycle regulatory proteins, thereby targeting them for destruction by the proteasome. This review describes our research aimed at understanding the structure and mechanism of the APC/C. We have determined the crystal structures of individual subunits and subcomplexes that provide atomic models to interpret density maps of the whole complex derived from single particle cryo-electron microscopy. With this information, we are generating pseudo-atomic models of functional states of the APC/C that provide insights into its overall architecture and mechanisms of substrate recognition, catalysis and regulation by inhibitory complexes.
authors.affiliation: Division of Structural Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK dbarford@mrc-lmb.cam.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Barford
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002453:Cell Cycle; D002875:Chromosomes; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae; D012568:Schizosaccharomyces; D054875:Ubiquitination
chemical_list: D064173:Anaphase-Promoting Complex-Cyclosome; D046988:Proteasome Endopeptidase Complex
keywords: anaphase-promoting complex or cyclosome; cell cycle; chromosome division