8E00

Symmetry expansion of yeast cytoplasmic dynein-1 bound to Lis1 in the chi conformation.

8E00 の概要

• エントリーDOI: 10.2210/pdb8e00/pdb
• 関連するPDBエントリー: 7MGM 8DZZ
• EMDBエントリー: 27810 27811
• 分子名称: Dynein heavy chain, cytoplasmic, Nuclear distribution protein PAC1, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: dynein, motor protein, transport
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 447533.98

構造登録者

Reimer, J.M.,Lahiri, I.,Leschziner, A.E. (登録日: 2022-08-08, 公開日: 2023-08-30, 最終更新日: 2023-09-27)

主引用文献

Karasmanis, E.P.,Reimer, J.M.,Kendrick, A.A.,Nguyen, K.H.V.,Rodriguez, J.A.,Truong, J.B.,Lahiri, I.,Reck-Peterson, S.L.,Leschziner, A.E.
Lis1 relieves cytoplasmic dynein-1 autoinhibition by acting as a molecular wedge.
Nat.Struct.Mol.Biol., 30:1357-1364, 2023

PubMed Abstract: Cytoplasmic dynein-1 transports intracellular cargo towards microtubule minus ends. Dynein is autoinhibited and undergoes conformational changes to form an active complex that consists of one or two dynein dimers, the dynactin complex, and activating adapter(s). The Lissencephaly 1 gene, LIS1, is genetically linked to the dynein pathway from fungi to mammals and is mutated in people with the neurodevelopmental disease lissencephaly. Lis1 is required for active dynein complexes to form, but how it enables this is unclear. Here, we present a structure of two yeast dynein motor domains with two Lis1 dimers wedged in-between. The contact sites between dynein and Lis1 in this structure, termed 'Chi,' are required for Lis1's regulation of dynein in Saccharomyces cerevisiae in vivo and the formation of active human dynein-dynactin-activating adapter complexes in vitro. We propose that this structure represents an intermediate in dynein's activation pathway, revealing how Lis1 relieves dynein's autoinhibited state.

PubMed: 37620585
DOI: 10.1038/s41594-023-01069-6

実験手法

ELECTRON MICROSCOPY (3.6 Å)