9E13

Full-length human dynein-1 in phi-like comformation bound to a Lis1 dimer under Lis1 condition

これはPDB形式変換不可エントリーです。

9E13 の概要

• エントリーDOI: 10.2210/pdb9e13/pdb
• EMDBエントリー: 47382
• 分子名称: Cytoplasmic dynein 1 heavy chain 1, MAGNESIUM ION, Cytoplasmic dynein 1 intermediate chain 2, ... (10 entities in total)
• 機能のキーワード: dynein-1, phi-like conformation, lis1, motor protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 1482257.40

構造登録者

Yang, J.,Zhang, K. (登録日: 2024-10-21, 公開日: 2025-08-06, 最終更新日: 2025-08-13)

主引用文献

Yang, J.,Zhao, Y.,Chai, P.,Yildiz, A.,Zhang, K.
Nde1 promotes Lis1 binding to full-length autoinhibited human dynein 1.
Nat.Chem.Biol., 2025

PubMed Abstract: Cytoplasmic dynein 1 (dynein) is the primary motor responsible for the retrograde transport of intracellular cargoes along microtubules. Activation of dynein requires the opening its autoinhibited Phi conformation, a process driven by Lis1 and Nde1/Ndel1. Using biochemical reconstitution and cryo-electron microscopy, we demonstrate that Nde1 enhances Lis1 binding to autoinhibited dynein and facilitates Phi opening. We identify a key intermediate in this activation pathway where a single Lis1 dimer binds between Phi-like (Phi) motor rings. In this 'Phi-Lis1' complex, Lis1 interacts with one motor domain through canonical sites at the AAA+ (adenosine triphosphatases associated with diverse cellular activities) ring and stalk, and with AAA5, AAA6 and linker regions of the other motor domain. Mutagenesis and motility assays confirm the critical role of the Phi-Lis1 interface in dynein activation. This intermediate forms rapidly in the presence of Nde1, although Nde1 is not part of Phi-Lis1. These findings provide key insights into how Nde1 promotes Lis1-mediated Phi opening.

PubMed: 40751002
DOI: 10.1038/s41589-025-01981-6

実験手法

ELECTRON MICROSCOPY (4.5 Å)