Science (American Association for the Advancement of Science), 2021-01, Vol.371 (6524), p.67-71
2021
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Details
- Autor(en) / Beteiligte
- Titel
- CDC20 assists its catalytic incorporation in the mitotic checkpoint complex
- Ist Teil von
- Science (American Association for the Advancement of Science), 2021-01, Vol.371 (6524), p.67-71
- Ort / Verlag
- United States: The American Association for the Advancement of Science
- Erscheinungsjahr
- 2021
- Quelle
- Science Online_科学在线
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.abc1152Titel-ID: cdi_proquest_miscellaneous_2474502389
- Format
- –
- Schlagworte
- Accuracy, Assembly, Biocatalysis, Catalysts, Catalytic converters, Cdc20 Proteins - metabolism, Cell Cycle Proteins - metabolism, Cell division, Chromosomes, HeLa Cells, Humans, Kinetochores, Kinetochores - metabolism, M Phase Cell Cycle Checkpoints, Mad2 Proteins - genetics, Mad2 Proteins - metabolism, Microtubules, Mitosis, Multiprotein Complexes - metabolism, Mutation, Phosphorylation, Poly-ADP-Ribose Binding Proteins - metabolism, Protein-Serine-Threonine Kinases, Proteins, Spindle Apparatus - metabolism, Substrates, Topology, Tracks (paths)