8FD6

Engineered human dynein motor domain in the microtubule-unbound state in the buffer containing ATP-Vi

8FD6 の概要

• エントリーDOI: 10.2210/pdb8fd6/pdb
• EMDBエントリー: 29003
• 分子名称: Cytoplasmic dynein 1 heavy chain 1,Serine--tRNA ligase, ADENOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: dynein, motor domain, microtubule-unbound, motor protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 359387.15

構造登録者

Ton, W.,Wang, Y.,Chai, P. (登録日: 2022-12-02, 公開日: 2023-06-21, 最終更新日: 2023-11-15)

主引用文献

Ton, W.D.,Wang, Y.,Chai, P.,Beauchamp-Perez, C.,Flint, N.T.,Lammers, L.G.,Xiong, H.,Zhang, K.,Markus, S.M.
Microtubule-binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport.
Nat.Struct.Mol.Biol., 30:1365-1379, 2023

PubMed Abstract: The lissencephaly-related protein LIS1 is a critical regulator of cytoplasmic dynein that governs motor function and intracellular localization (for example, to microtubule plus-ends). Although LIS1 binding is required for dynein activity, its unbinding prior to initiation of cargo transport is equally important, since preventing dissociation leads to dynein dysfunction. To understand whether and how dynein-LIS1 binding is modulated, we engineered dynein mutants locked in a microtubule-bound (MT-B) or microtubule-unbound (MT-U) state. Whereas the MT-B mutant exhibits low LIS1 affinity, the MT-U mutant binds LIS1 with high affinity, and as a consequence remains almost irreversibly associated with microtubule plus-ends. We find that a monomeric motor domain is sufficient to exhibit these opposing LIS1 affinities, and that this is evolutionarily conserved between yeast and humans. Three cryo-EM structures of human dynein with and without LIS1 reveal microtubule-binding induced conformational changes responsible for this regulation. Our work reveals key biochemical and structural insight into LIS1-mediated dynein activation.

PubMed: 37322240
DOI: 10.1038/s41594-023-01010-x

実験手法

ELECTRON MICROSCOPY (2.9 Å)