3J8A

Structure of the F-actin-tropomyosin complex

3J8A の概要

• エントリーDOI: 10.2210/pdb3j8a/pdb
• EMDBエントリー: 6124
• 分子名称: tropomyosin alpha-1, Actin, alpha skeletal muscle, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: contractile filament, muscle, thin filament, cytoskeleton, structural protein-hydrolase complex, structural protein/hydrolase
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 234650.05

構造登録者

von der Ecken, J.,Mueller, M.,Lehman, W.,Manstein, J.M.,Penczek, A.P.,Raunser, S. (登録日: 2014-10-08, 公開日: 2014-12-10, 最終更新日: 2025-03-26)

主引用文献

von der Ecken, J.,Muller, M.,Lehman, W.,Manstein, D.J.,Penczek, P.A.,Raunser, S.
Structure of the F-actin--tropomyosin complex.
Nature, 519:114-117, 2015

PubMed Abstract: Filamentous actin (F-actin) is the major protein of muscle thin filaments, and actin microfilaments are the main component of the eukaryotic cytoskeleton. Mutations in different actin isoforms lead to early-onset autosomal dominant non-syndromic hearing loss, familial thoracic aortic aneurysms and dissections, and multiple variations of myopathies. In striated muscle fibres, the binding of myosin motors to actin filaments is mainly regulated by tropomyosin and troponin. Tropomyosin also binds to F-actin in smooth muscle and in non-muscle cells and stabilizes and regulates the filaments there in the absence of troponin. Although crystal structures for monomeric actin (G-actin) are available, a high-resolution structure of F-actin is still missing, hampering our understanding of how disease-causing mutations affect the function of thin muscle filaments and microfilaments. Here we report the three-dimensional structure of F-actin at a resolution of 3.7 Å in complex with tropomyosin at a resolution of 6.5 Å, determined by electron cryomicroscopy. The structure reveals that the D-loop is ordered and acts as a central region for hydrophobic and electrostatic interactions that stabilize the F-actin filament. We clearly identify map density corresponding to ADP and Mg(2+) and explain the possible effect of prominent disease-causing mutants. A comparison of F-actin with G-actin reveals the conformational changes during filament formation and identifies the D-loop as their key mediator. We also confirm that negatively charged tropomyosin interacts with a positively charged groove on F-actin. Comparison of the position of tropomyosin in F-actin-tropomyosin with its position in our previously determined F-actin-tropomyosin-myosin structure reveals a myosin-induced transition of tropomyosin. Our results allow us to understand the role of individual mutations in the genesis of actin- and tropomyosin-related diseases and will serve as a strong foundation for the targeted development of drugs.

PubMed: 25470062
DOI: 10.1038/nature14033

実験手法

ELECTRON MICROSCOPY (3.7 Å)