7RSQ

Cryo-EM structure of KIFBP core

7RSQ の概要

• エントリーDOI: 10.2210/pdb7rsq/pdb
• EMDBエントリー: 24677
• 分子名称: KIF-binding protein (1 entity in total)
• 機能のキーワード: kinesin regulation protein, motor protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 71913.95

構造登録者

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. (登録日: 2021-08-11, 公開日: 2021-09-08, 最終更新日: 2024-06-05)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.8 Å)