6VPP

Cryo-EM structure of microtubule-bound KLP61F motor with tail domain in the nucleotide-free state

6VPP の概要

• エントリーDOI: 10.2210/pdb6vpp/pdb
• EMDBエントリー: 21314 21315
• 分子名称: Tubulin alpha-1A chain, Tubulin beta chain, Kinesin-like protein Klp61F, ... (6 entities in total)
• 機能のキーワード: kinesin-5, klp61f, microtubules, mitotic spindles, nucleotide-free state, cell cycle, motor protein
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 143647.06

構造登録者

Bodrug, T.,Wilson-Kubalek, E.M.,Nithianantham, S.,Debs, G.,Sindelar, C.V.,Milligan, R.,Al-Bassam, J. (登録日: 2020-02-04, 公開日: 2020-02-19, 最終更新日: 2024-03-06)

主引用文献

Bodrug, T.,Wilson-Kubalek, E.M.,Nithianantham, S.,Thompson, A.F.,Alfieri, A.,Gaska, I.,Major, J.,Debs, G.,Inagaki, S.,Gutierrez, P.,Gheber, L.,McKenney, R.J.,Sindelar, C.V.,Milligan, R.,Stumpff, J.,Rosenfeld, S.S.,Forth, S.T.,Al-Bassam, J.
The kinesin-5 tail domain directly modulates the mechanochemical cycle of the motor domain for anti-parallel microtubule sliding.
Elife, 9:-, 2020

PubMed Abstract: Kinesin-5 motors organize mitotic spindles by sliding apart microtubules. They are homotetramers with dimeric motor and tail domains at both ends of a bipolar minifilament. Here, we describe a regulatory mechanism involving direct binding between tail and motor domains and its fundamental role in microtubule sliding. Kinesin-5 tails decrease microtubule-stimulated ATP-hydrolysis by specifically engaging motor domains in the nucleotide-free or ADP states. Cryo-EM reveals that tail binding stabilizes an open motor domain ATP-active site. Full-length motors undergo slow motility and cluster together along microtubules, while tail-deleted motors exhibit rapid motility without clustering. The tail is critical for motors to zipper together two microtubules by generating substantial sliding forces. The tail is essential for mitotic spindle localization, which becomes severely reduced in tail-deleted motors. Our studies suggest a revised microtubule-sliding model, in which kinesin-5 tails stabilize motor domains in the microtubule-bound state by slowing ATP-binding, resulting in high-force production at both homotetramer ends.

PubMed: 31958056
DOI: 10.7554/eLife.51131

実験手法

ELECTRON MICROSCOPY (4.4 Å)