6TA4

Human kinesin-5 motor domain in the AMPPNP state bound to microtubules

6TA4 の概要

• エントリーDOI: 10.2210/pdb6ta4/pdb
• EMDBエントリー: 10422
• 分子名称: Tubulin beta chain, Tubulin alpha-1B chain, Kinesin-like protein KIF11, ... (7 entities in total)
• 機能のキーワード: kinesin, microtubule, mitosis, inhibition, motor, cell cycle
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 142244.21

構造登録者

Pena, A.P.,Sweeney, A.,Cook, A.D.,Moores, C.A.,Topf, M. (登録日: 2019-10-29, 公開日: 2020-03-04, 最終更新日: 2024-05-22)

主引用文献

Pena, A.,Sweeney, A.,Cook, A.D.,Topf, M.,Moores, C.A.
Structure of Microtubule-Trapped Human Kinesin-5 and Its Mechanism of Inhibition Revealed Using Cryoelectron Microscopy.
Structure, 28:450-457.e5, 2020

PubMed Abstract: Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism of the human kinesin-5 inhibitor GSK-1, which allosterically promotes tight microtubule binding. GSK-1 inhibits monomeric human kinesin-5 ATPase and microtubule gliding activities, and promotes the motor's microtubule stabilization activity. Using cryoelectron microscopy, we determined the 3D structure of the microtubule-bound motor-GSK-1 at 3.8 Å overall resolution. The structure reveals that GSK-1 stabilizes the microtubule binding surface of the motor in an ATP-like conformation, while destabilizing regions of the motor around the empty nucleotide binding pocket. Density corresponding to GSK-1 is located between helix-α4 and helix-α6 in the motor domain at its interface with the microtubule. Using a combination of difference mapping and protein-ligand docking, we characterized the kinesin-5-GSK-1 interaction and further validated this binding site using mutagenesis. This work opens up new avenues of investigation of kinesin inhibition and spindle perturbation.

PubMed: 32084356
DOI: 10.1016/j.str.2020.01.013

実験手法

ELECTRON MICROSCOPY (6.1 Å)