Cryo-EM visualizes multiple steps of dynein's activation pathway.

ABSTRACT: Cytoplasmic dynein-1 (dynein) is an essential molecular motor controlled in part by autoinhibition. We recently identified a structure of partially autoinhibited dynein bound to Lis1, a key dynein regulator mutated in the neurodevelopmental disease lissencephaly. This structure provides an intermediate state in dynein's activation pathway; however, other structural information is needed to fully explain Lis1 function in dynein activation. Here, we used cryo-EM and samples incubated with ATP for different times to reveal novel conformations that we propose represent intermediate states in the dynein's activation pathway. We solved sixteen high-resolution structures, including seven distinct dynein and dynein-Lis1 structures from the same sample. Our data also support a model in which Lis1 r

SUBMITTER: Kendrick AA 

PROVIDER: S-EPMC11482813 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature