9ZZI

Cryo-EM structure of F-actin in the ADP state

9ZZI の概要

• エントリーDOI: 10.2210/pdb9zzi/pdb
• EMDBエントリー: 74998
• 分子名称: Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: actin, f-actin, structural protein
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 211635.70

構造登録者

Brotzman, S.B.,Palmer, N.J.,Dominguez, R. (登録日: 2026-01-07, 公開日: 2026-06-24, 最終更新日: 2026-08-05)

主引用文献

Brotzman, S.B.,Palmer, N.J.,Boczkowska, M.,Dominguez, R.
Mechanism of actin thin filament pointed-end elongation by leiomodin.
Nat Commun, 17:-, 2026

PubMed Abstract: In non-muscle cells, actin filaments exhibit variable lengths and rapid turnover, with subunits adding primarily at the barbed end. The situation is strikingly different in striated muscle sarcomeres, where despite rapid turnover, actin thin filaments exhibit uniform length and exchange subunits primarily at the pointed end. This filament length uniformity is tightly regulated by several proteins, including the molecular ruler nebulin in skeletal muscle and the barbed- and pointed-end capping proteins CapZ and tropomodulin (Tmod) in both skeletal and cardiac muscles. Recent studies in cells and animal models have identified leiomodin-2 (Lmod2) as an additional regulator proposed to promote pointed-end elongation to maintain thin filament length. This activity would make leiomodin the only known eukaryotic factor to drive pointed-end elongation, yet its molecular mechanism remains unresolved. Here, we present a series of cryo-electron microscopy structures that support a stepwise elongation mechanism in which two Lmod2 molecules alternate at the pointed end while recruiting actin monomers. These findings establish the molecular basis of pointed-end elongation in muscle sarcomeres and provide a framework for understanding mutations in Lmod2 that cause dilated cardiomyopathy.

PubMed: 42477379
DOI: 10.1038/s41467-026-74810-6

実験手法

ELECTRON MICROSCOPY (2.06 Å)