6RFD

Cryo-EM structure of the N-terminal DC repeat (NDC) of NDC-NDC chimera (human sequence) bound to 14-protofilament GDP-microtubule

6RFD の概要

• エントリーDOI: 10.2210/pdb6rfd/pdb
• EMDBエントリー: 4863
• 分子名称: Tubulin alpha-1B chain, Tubulin beta-2B chain, Neuronal migration protein doublecortin, ... (6 entities in total)
• 機能のキーワード: microtubule-associated protein chimera, ubiquitin-like fold, microtubule stabilisation, cytosolic protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 206176.65

構造登録者

Manka, S.W. (登録日: 2019-04-12, 公開日: 2020-05-13, 最終更新日: 2024-05-22)

主引用文献

Manka, S.W.,Moores, C.A.
Pseudo-repeats in doublecortin make distinct mechanistic contributions to microtubule regulation.
Embo Rep., 21:e51534-e51534, 2020

PubMed Abstract: Doublecortin (DCX) is a neuronal microtubule-associated protein (MAP) indispensable for brain development. Its flexibly linked doublecortin (DC) domains-NDC and CDC-mediate microtubule (MT) nucleation and stabilization, but it is unclear how. Using high-resolution time-resolved cryo-EM, we mapped NDC and CDC interactions with tubulin at different MT polymerization stages and studied their functional effects on MT dynamics using TIRF microscopy. Although coupled, each DC repeat within DCX appears to have a distinct role in MT nucleation and stabilization: CDC is a conformationally plastic module that appears to facilitate MT nucleation and stabilize tubulin-tubulin contacts in the nascent MT lattice, while NDC appears to be favored along the mature lattice, providing MT stabilization. Our structures of MT-bound DC domains also explain in unprecedented detail the DCX mutation-related brain defects observed in the clinic. This modular composition of DCX reflects a common design principle among MAPs where pseudo-repeats of tubulin/MT binding elements chaperone or stabilize distinct conformational transitions to regulate distinct stages of MT dynamic instability.

PubMed: 33051979
DOI: 10.15252/embr.202051534

実験手法

ELECTRON MICROSCOPY (3.9 Å)