9E22

Cryo-EM structure of human cytoplasmic dynein-1 bound to LIS1 in the presence of ATP

Summary for 9E22

• Entry DOI: 10.2210/pdb9e22/pdb
• Related: 9DZY 9E0K 9E0T 9E0U 9E0W 9E0X 9E0Y
• EMDB information: 47342 47360 47370 47371 47372 47373 47377 47429
• Descriptor: Cytoplasmic dynein 1 heavy chain 1, Platelet-activating factor acetylhydrolase IB subunit beta, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: human, motor protein, complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 602742.24

Authors

Nguyen, K.H.V.,Kendrick, A.A.,Leschziner, A.E. (deposition date: 2024-10-21, release date: 2025-07-09, Last modification date: 2026-01-21)

Primary citation

Nguyen, K.H.V.,Karasmanis, E.P.,Kendrick, A.A.,Reck-Peterson, S.L.,Leschziner, A.E.
Cryo-EM captures early intermediate steps in dynein activation by LIS1.
Nat Commun, 16:7054-7054, 2025

PubMed Abstract: Cytoplasmic dynein-1 (dynein) is an essential molecular motor in eukaryotic cells. Dynein primarily exists in an autoinhibited Phi state and requires conformational changes to assemble with its cofactors and form active transport complexes. LIS1, a key dynein regulator, enhances dynein activation and assembly. Using cryo-EM and a human dynein-LIS1 sample incubated with ATP, we map the conformational landscape of dynein activation by LIS1 and identify an early intermediate state that we propose precedes the previously identified dynein-LIS1 Chi state. Mutations that disrupt this species, which we termed "Pre-Chi", lead to motility defects in vitro, emphasizing its functional importance. Together, our findings provide insights into how LIS1 relieves dynein autoinhibition during the activation pathway.

PubMed: 40750582
DOI: 10.1038/s41467-025-62185-z

Experimental method

ELECTRON MICROSCOPY (3.3 Å)