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-Structure paper
タイトル | Cryo-EM Reveals How Human Cytoplasmic Dynein Is Auto-inhibited and Activated. |
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ジャーナル・号・ページ | Cell, Vol. 169, Issue 7, Page 1303-1314.e18, Year 2017 |
掲載日 | 2017年6月15日 |
著者 | Kai Zhang / Helen E Foster / Arnaud Rondelet / Samuel E Lacey / Nadia Bahi-Buisson / Alexander W Bird / Andrew P Carter / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:28602352 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 - 15.0 Å |
構造データ | EMDB-3698: motor domain of complete human dynein-1 in the state of phi-particle EMDB-3703: Human cytoplasmic dynein-1 tail in the twisted state EMDB-3704: EMDB-3705, PDB-5nvu: EMDB-3706, PDB-5nw4: EMDB-3707: |
化合物 | ChemComp-ADP: ChemComp-ATP: ChemComp-MG: |
由来 |
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キーワード | MOTOR PROTEIN / dynein / motor domain / AAA+ / tail complex / dynein-1 / phi-particle / dynactin / BICD |