5VH9

Cryo-EM structure of yeast cytoplasmic dynein-1 with Lis1 and ATP

5VH9 の概要

• エントリーDOI: 10.2210/pdb5vh9/pdb
• 関連するPDBエントリー: 5VLJ
• EMDBエントリー: 8673 8706
• 分子名称: Dynein heavy chain, cytoplasmic, Nuclear distribution protein PAC1 (2 entities in total)
• 機能のキーワード: cytoplasmic dynein, lis1, motor protein
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 313311.70

構造登録者

Cianfrocco, M.A.,DeSantis, M.E.,Htet, Z.M.,Tran, P.T.,Reck-Peterson, S.L.,Leschziner, A.E. (登録日: 2017-04-12, 公開日: 2017-09-06, 最終更新日: 2024-10-23)

主引用文献

DeSantis, M.E.,Cianfrocco, M.A.,Htet, Z.M.,Tran, P.T.,Reck-Peterson, S.L.,Leschziner, A.E.
Lis1 Has Two Opposing Modes of Regulating Cytoplasmic Dynein.
Cell, 170:1197-1208.e12, 2017

PubMed Abstract: Regulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a conserved regulator of dynein, binds to its motor domain and induces a tight microtubule-binding state in dynein. The work we present here-a combination of biochemistry, single-molecule assays, and cryoelectron microscopy-led to the surprising discovery that Lis1 has two opposing modes of regulating dynein, being capable of inducing both low and high affinity for the microtubule. We show that these opposing modes depend on the stoichiometry of Lis1 binding to dynein and that this stoichiometry is regulated by the nucleotide state of dynein's AAA3 domain. The low-affinity state requires Lis1 to also bind to dynein at a novel conserved site, mutation of which disrupts Lis1's function in vivo. We propose a new model for the regulation of dynein by Lis1.

PubMed: 28886386
DOI: 10.1016/j.cell.2017.08.037

実験手法

ELECTRON MICROSCOPY (7.7 Å)