EMD-24677
Cryo-EM structure of KIFBP core
EMD-24677
Single-particle3.8 Å

Map released: 08/09/2021
Last modified: 05/06/2024
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
Sample: high-resolution structure of KIFBP(core)
Fitted models: 7rsq (Avg. Q-score: 0.4)
Deposition Authors: Solon AL


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









(2021) Sci Adv , 7 , eabj9812 - eabj9812
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.
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.