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Understanding the structural basis for controlling chromosome division
#MMPMID25624511
Barford D
Philos Trans A Math Phys Eng Sci
2015[Mar]; 373
(2036
): ? PMID25624511
show ga
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.
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