5nvu

Full length human cytoplasmic dynein-1 in the phi-particle conformation

Loading... Status: waiting for Mol* initialization Structural highlights 5nvu is a 13 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 15Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Cryo-EM Reveals How Human Cytoplasmic Dynein Is Auto-inhibited and Activated.,Zhang K, Foster HE, Rondelet A, Lacey SE, Bahi-Buisson N, Bird AW, Carter AP Cell. 2017 Jun 15;169(7):1303-1314.e18. doi: 10.1016/j.cell.2017.05.025. Epub, 2017 Jun 8. PMID:28602352 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dynein 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA