5NVS

Human cytoplasmic dynein-1 tail in the twisted N-terminus state

Summary for 5NVS

• Entry DOI: 10.2210/pdb5nvs/pdb
• EMDB information: 3698 3703
• Descriptor: dynein heavy chain, Tctex, intermediate chain, ... (13 entities in total)
• Functional Keywords: motor protein, dynein, tail complex
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 16
• Total formula weight: 344110.24

Authors

Zhang, K.,Foster, H.E.,Carter, A.P. (deposition date: 2017-05-04, release date: 2017-06-28, Last modification date: 2024-07-10)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (8.4 Å)