5NUG

Motor domains from human cytoplasmic dynein-1 in the phi-particle conformation

5NUG の概要

• エントリーDOI: 10.2210/pdb5nug/pdb
• EMDBエントリー: 3698
• 分子名称: Cytoplasmic dynein 1 heavy chain 1, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: motor protein, dynein, motor domain, aaa+
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 1069792.68

構造登録者

Zhang, K.,Foster, H.E.,Carter, A.P. (登録日: 2017-04-30, 公開日: 2017-06-28, 最終更新日: 2024-05-15)

主引用文献

Zhang, K.,Foster, H.E.,Rondelet, A.,Lacey, S.E.,Bahi-Buisson, N.,Bird, A.W.,Carter, A.P.
Cryo-EM Reveals How Human Cytoplasmic Dynein Is Auto-inhibited and Activated.
Cell, 169:1303-1314.e18, 2017

PubMed Abstract: Cytoplasmic dynein-1 binds dynactin and cargo adaptor proteins to form a transport machine capable of long-distance processive movement along microtubules. However, it is unclear why dynein-1 moves poorly on its own or how it is activated by dynactin. Here, we present a cryoelectron microscopy structure of the complete 1.4-megadalton human dynein-1 complex in an inhibited state known as the phi-particle. We reveal the 3D structure of the cargo binding dynein tail and show how self-dimerization of the motor domains locks them in a conformation with low microtubule affinity. Disrupting motor dimerization with structure-based mutagenesis drives dynein-1 into an open form with higher affinity for both microtubules and dynactin. We find the open form is also inhibited for movement and that dynactin relieves this by reorienting the motor domains to interact correctly with microtubules. Our model explains how dynactin binding to the dynein-1 tail directly stimulates its motor activity.

PubMed: 28602352
DOI: 10.1016/j.cell.2017.05.025

実験手法

ELECTRON MICROSCOPY (3.8 Å)