CDC20 assists its catalytic incorporation in the mitotic checkpoint complex.
Biocatalysis
Cdc20 Proteins
/ metabolism
Cell Cycle Proteins
/ metabolism
HeLa Cells
Humans
Kinetochores
/ metabolism
M Phase Cell Cycle Checkpoints
Mad2 Proteins
/ genetics
Multiprotein Complexes
/ metabolism
Mutation
Poly-ADP-Ribose Binding Proteins
/ metabolism
Protein Serine-Threonine Kinases
Spindle Apparatus
/ metabolism
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
received:
07
04
2020
accepted:
18
11
2020
entrez:
1
1
2021
pubmed:
2
1
2021
medline:
12
2
2021
Statut:
ppublish
Résumé
Open (O) and closed (C) topologies of HORMA-domain proteins are respectively associated with inactive and active states of fundamental cellular pathways. The HORMA protein O-MAD2 converts to C-MAD2 upon binding CDC20. This is rate limiting for assembly of the mitotic checkpoint complex (MCC), the effector of a checkpoint required for mitotic fidelity. A catalyst assembled at kinetochores accelerates MAD2:CDC20 association through a poorly understood mechanism. Using a reconstituted SAC system, we discovered that CDC20 is an impervious substrate for which access to MAD2 requires simultaneous docking on several sites of the catalytic complex. Our analysis indicates that the checkpoint catalyst is substrate assisted and promotes MCC assembly through spatially and temporally coordinated conformational changes in both MAD2 and CDC20. This may define a paradigm for other HORMA-controlled systems.
Identifiants
pubmed: 33384373
pii: 371/6524/67
doi: 10.1126/science.abc1152
doi:
Substances chimiques
BUB3 protein, human
0
Cdc20 Proteins
0
Cell Cycle Proteins
0
MAD2L1 protein, human
0
Mad2 Proteins
0
Multiprotein Complexes
0
Poly-ADP-Ribose Binding Proteins
0
CDC20 protein, human
156288-95-8
BUB1 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-71Informations de copyright
Copyright © 2021, American Association for the Advancement of Science.