9YNF

Motor domain of human dynein-1 in post1 state

9YNF の概要

• エントリーDOI: 10.2210/pdb9ynf/pdb
• EMDBエントリー: 73176
• 分子名称: Cytoplasmic dynein 1 heavy chain 1, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: dynein-1, motor protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 534975.33

構造登録者

Yang, J.,Rao, Q.,Chai, P.,Zhang, K. (登録日: 2025-10-10, 公開日: 2026-01-28, 最終更新日: 2026-04-08)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.92 Å)