Nde1 Promotes Lis1 Binding to Full-Length Autoinhibited Human Dynein-1.

ABSTRACT: Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi. We discover a key intermediate step in the dynein activation pathway where a single Lis1 dimer binds between the Phi-like (Phi^L) motor rings of dynein. In this "Phi^L-Lis1", Lis1 interacts with one of the motor domains through its canonical interaction sites at the AAA+ ring and stalk and binds to

SUBMITTER: Yang J 

PROVIDER: S-EPMC11722290 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature