EMD-24677

Single-particle
3.8 Å
EMD-24677 Deposition: 11/08/2021
Map released: 08/09/2021
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-24677

Cryo-EM structure of KIFBP core

EMD-24677

Single-particle
3.8 Å
EMD-24677 Deposition: 11/08/2021
Map released: 08/09/2021
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: high-resolution structure of KIFBP(core)
Fitted models: 7rsq (Avg. Q-score: 0.4)

Deposition Authors: Solon AL , Tan Z
Kinesin-binding protein remodels the kinesin motor to prevent microtubule binding.
Solon AL , Tan Z , Schutt KL , Jepsen L, Haynes SE , Nesvizhskii AI , Sept D , Stumpff J , Ohi R , Cianfrocco MA
(2021) Sci Adv , 7 , eabj9812 - eabj9812
PUBMED: 34797717
DOI: doi:10.1126/sciadv.abj9812
ISSN: 2375-2548
Abstract:
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.