Kinesin-binding protein remodels the kinesin motor to prevent microtubule binding.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
19 Nov 2021
19 Nov 2021
Historique:
entrez:
19
11
2021
pubmed:
20
11
2021
medline:
20
11
2021
Statut:
ppublish
Résumé
Kinesins are regulated in space and time to ensure activation only in the presence of cargo. Kinesin-binding protein (KIFBP), which is mutated in Goldberg-Shprintzen syndrome, binds to and inhibits the catalytic motor heads of 8 of 45 kinesin superfamily members, but the mechanism remains poorly defined. Here, we used cryo–electron microscopy and cross-linking mass spectrometry to determine high-resolution structures of KIFBP alone and in complex with two mitotic kinesins, revealing structural remodeling of kinesin by KIFBP. We find that KIFBP remodels kinesin motors and blocks microtubule binding (i) via allosteric changes to kinesin and (ii) by sterically blocking access to the microtubule. We identified two regions of KIFBP necessary for kinesin binding and cellular regulation during mitosis. Together, this work further elucidates the molecular mechanism of KIFBP-mediated kinesin inhibition and supports a model in which structural rearrangement of kinesin motor domains by KIFBP abrogates motor protein activity.
Identifiants
pubmed: 34797717
doi: 10.1126/sciadv.abj9812
pmc: PMC8604404
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabj9812Subventions
Organisme : NIGMS NIH HHS
ID : K12 GM111725
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM094231
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121491
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM136822
Pays : United States
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