9YNE

Motor domain of human dynein-1 in pre-power stroke bound to dynactin-p150glued-CC1B-ICD and LIS1

This is a non-PDB format compatible entry.

Summary for 9YNE

• Entry DOI: 10.2210/pdb9yne/pdb
• EMDB information: 73175
• Descriptor: Cytoplasmic dynein 1 heavy chain 1, ADENOSINE-5'-TRIPHOSPHATE, Platelet-activating factor acetylhydrolase IB subunit beta, ... (10 entities in total)
• Functional Keywords: dynein-1, lis1, p150glued, motor protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 1155325.42

Authors

Yang, J.,Rao, Q.,Chai, P.,Zhang, K. (deposition date: 2025-10-10, release date: 2026-01-28, Last modification date: 2026-04-08)

Primary citation

Rao, Q.,Yang, J.,Chai, P.,Markus, S.,Zhang, K.
Roles of microtubules and LIS1 in dynein transport machinery assembly.
Nature, 2026

PubMed Abstract: Cytoplasmic dynein-1, a microtubule (MT)-based motor protein, requires dynactin and a coiled-coil adaptor to form the processive dynein-dynactin-adaptor (DDA) complex. The roles of MTs and dynein regulator lissencephaly-1 (LIS1) in DDA assembly have remained elusive. Here we use cryo-electron microscopy to determine the structural basis of MT- and LIS1-mediated DDA assembly. We show that an adaptor-independent dynein-dynactin complex spontaneously forms on MTs with an intrinsic 2:1 stoichiometry in a highly efficient manner, driven by parallel alignment of dynein tails upon MT binding. Adaptors can wedge into and exchange within the assembled MT-bound dynein-dynactin complex; these processes are enabled by relative rotations between dynein and dynactin and facilitated by the dynein light-intermediate chains that assist the adaptor 'search' mechanism. Although LIS1 is dispensable for efficient DD(A)-MT assembly, its presence expands the conformational landscape of DD(A) assemblies on MTs. Cryo-electron microscopy reveals that LIS1 bridges dynactin p150 and dynein in both the closed Phi-like and open prepowerstroke states, stabilizing low-MT-affinity intermediates that tether dynein molecules in proximity to MTs and prime them for subsequent DD(A) assembly through alternative pathways. These findings demonstrate the dynamic adaptability of the dynein transport machinery and the coordinated roles of MTs and LIS1 in DDA assembly.

PubMed: 41708859
DOI: 10.1038/s41586-026-10153-y

Experimental method

ELECTRON MICROSCOPY (8.46 Å)