5NUG

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

Summary for 5NUG

• Entry DOI: 10.2210/pdb5nug/pdb
• EMDB information: 3698
• Descriptor: Cytoplasmic dynein 1 heavy chain 1, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: motor protein, dynein, motor domain, aaa+
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 1069792.68

Authors

Zhang, K.,Foster, H.E.,Carter, A.P. (deposition date: 2017-04-30, release date: 2017-06-28, Last modification date: 2024-05-15)

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 (3.8 Å)