6MZG

Structural Basis of Tubulin Recruitment and Assembly by Microtubule Polymerases with Tumor Overexpressed Gene (TOG) Domain Arrays

6MZG の概要

• エントリーDOI: 10.2210/pdb6mzg/pdb
• 関連するPDBエントリー: 6MZE 6MZF
• 分子名称: Tubulin alpha-1A chain, Tubulin beta chain, Protein Stu2p/Alp14p, ... (7 entities in total)
• 機能のキーワード: microtubule, tubulin, tubulin polymerization, heat repeats, microtubule polymerase, protofilament, tog arrays, and unfurled assembly., cell cycle
• 由来する生物種: Lachancea kluyveri NRRL Y-12651; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 560372.55

構造登録者

Nithianantham, S.,Al-Bassam, J. (登録日: 2018-11-05, 公開日: 2018-11-28, 最終更新日: 2024-03-13)

主引用文献

Nithianantham, S.,Cook, B.D.,Beans, M.,Guo, F.,Chang, F.,Al-Bassam, J.
Structural basis of tubulin recruitment and assembly by microtubule polymerases with Tumor Overexpressed Gene (TOG) domain arrays.
Elife, 7:-, 2018

PubMed Abstract: XMAP215/Stu2/Alp14 proteins accelerate microtubule plus-end polymerization by recruiting tubulins via arrays of tumor overexpressed gene (TOG) domains, yet their mechanism remains unknown. Here, we describe the biochemical and structural basis for TOG arrays in recruiting and polymerizing tubulins. Alp14 binds four tubulins via dimeric TOG1-TOG2 subunits, in which each domain exhibits a distinct exchange rate for tubulin. X-ray structures revealed square-shaped assemblies composed of pseudo-dimeric TOG1-TOG2 subunits assembled head-to-tail, positioning four unpolymerized tubulins in a polarized wheel-like configuration. Crosslinking and electron microscopy show Alp14-tubulin forms square assemblies in solution, and inactivating their interfaces destabilize this organization without influencing tubulin binding. An X-ray structure determined using approach to modulate tubulin polymerization revealed an unfurled assembly, in which TOG1-TOG2 uniquely bind to two polymerized tubulins. Our findings suggest a new microtubule polymerase model in which TOG arrays recruit tubulins by forming square assemblies that then unfurl, facilitating their concerted polymerization into protofilaments.

PubMed: 30422110
DOI: 10.7554/eLife.38922

実験手法

X-RAY DIFFRACTION (3.208 Å)