6EVX

Cryo-EM structure of GDP.Pi-microtubule rapidly co-polymerised with doublecortin

6EVX の概要

• エントリーDOI: 10.2210/pdb6evx/pdb
• EMDBエントリー: 3961 3962
• 分子名称: Tubulin beta chain, Tubulin alpha-1B chain, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: microtubule, gtpase, tubulin, structural protein
• 由来する生物種: Sus scrofa (Pig); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 607187.23

構造登録者

Manka, S.W. (登録日: 2017-11-03, 公開日: 2018-07-11, 最終更新日: 2024-05-15)

主引用文献

Manka, S.W.,Moores, C.A.
The role of tubulin-tubulin lattice contacts in the mechanism of microtubule dynamic instability.
Nat. Struct. Mol. Biol., 25:607-615, 2018

PubMed Abstract: Microtubules form from longitudinally and laterally assembling tubulin α-β dimers. The assembly induces strain in tubulin, resulting in cycles of microtubule catastrophe and regrowth. This 'dynamic instability' is governed by GTP hydrolysis that renders the microtubule lattice unstable, but it is unclear how. We used a human microtubule nucleating and stabilizing neuronal protein, doublecortin, and high-resolution cryo-EM to capture tubulin's elusive hydrolysis intermediate GDP•Pi state, alongside the prehydrolysis analog GMPCPP state and the posthydrolysis GDP state with and without an anticancer drug, Taxol. GTP hydrolysis to GDP•Pi followed by Pi release constitutes two distinct structural transitions, causing unevenly distributed compressions of tubulin dimers, thereby tightening longitudinal and loosening lateral interdimer contacts. We conclude that microtubule catastrophe is triggered because the lateral contacts can no longer counteract the strain energy stored in the lattice, while reinforcement of the longitudinal contacts may support generation of force.

PubMed: 29967541
DOI: 10.1038/s41594-018-0087-8

実験手法

ELECTRON MICROSCOPY (4.2 Å)