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-Structure paper
| タイトル | Roles of microtubules and LIS1 in dynein transport machinery assembly. |
|---|---|
| ジャーナル・号・ページ | Nature, Year 2026 |
| 掲載日 | 2026年2月18日 |
著者 | Qinhui Rao / Jun Yang / Pengxin Chai / Steven Markus / Kai Zhang / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:41708859 |
| 手法 | EM (単粒子) |
| 解像度 | 3.5 - 15.0 Å |
| 構造データ | EMDB-46843, PDB-9dgp: EMDB-46844, PDB-9dgq: EMDB-46845, PDB-9dgr: EMDB-46846, PDB-9dgs: EMDB-46847, PDB-9dgt: EMDB-46848, PDB-9dgu: EMDB-46849, PDB-9dgv: ![]() EMDB-47061: Consensus map of dynein-dynactin on microtubules EMDB-73173, PDB-9ync: EMDB-73174, PDB-9ynd: EMDB-73175, PDB-9yne: EMDB-73176, PDB-9ynf: EMDB-73178, PDB-9yng: EMDB-73179, PDB-9ynh: |
| 化合物 | ![]() ChemComp-ADP: ![]() ChemComp-ATP: ![]() ChemComp-ANP: ![]() ChemComp-MG: ![]() ChemComp-ZN: |
| 由来 |
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キーワード | MOTOR PROTEIN / dynein / microtubule / dynactin / BICDR / TRAK2 / Dynein-1 / phi-like conformation / Lis1 / p150glued / p150 |
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