7RSI

The cryo-EM map of KIF18A bound to KIFBP

Summary for 7RSI

• Entry DOI: 10.2210/pdb7rsi/pdb
• EMDB information: 24672
• Descriptor: KIF-binding protein, Kinesin-like protein KIF18A, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: kinesin regualtion protein, motor protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 111925.46

Authors

Tan, Z.,Solon, A.L.,Schutt, K.L.,Jepsen, L.,Haynes, S.E.,Nesvizhskii, A.I.,Sept, D.,Stumpff, J.,Ohi, R.,Cianfrocco, M.A. (deposition date: 2021-08-11, release date: 2021-09-08, Last modification date: 2024-06-05)

Primary citation

Solon, A.L.,Tan, Z.,Schutt, K.L.,Jepsen, L.,Haynes, S.E.,Nesvizhskii, A.I.,Sept, D.,Stumpff, J.,Ohi, R.,Cianfrocco, M.A.
Kinesin-binding protein remodels the kinesin motor to prevent microtubule binding.
Sci Adv, 7:eabj9812-eabj9812, 2021

PubMed 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.

PubMed: 34797717
DOI: 10.1126/sciadv.abj9812

Experimental method

ELECTRON MICROSCOPY (4.9 Å)