7R91

cryo-EM structure of the rigor state wild type myosin-15-F-actin complex

7R91 の概要

• エントリーDOI: 10.2210/pdb7r91/pdb
• EMDBエントリー: 24321 24322
• 分子名称: Actin, alpha skeletal muscle, intermediate form, Isoform 3 of Unconventional myosin-XV, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: myosin motor proteins, actin cytoskeleton, stereocilia, deafness, motor protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 204431.51

構造登録者

Gong, R.,Reynolds, M.J.,Gurel, P.,Alushin, G.M. (登録日: 2021-06-28, 公開日: 2021-07-28, 最終更新日: 2022-08-03)

主引用文献

Gong, R.,Jiang, F.,Moreland, Z.G.,Reynolds, M.J.,de Los Reyes, S.E.,Gurel, P.,Shams, A.,Heidings, J.B.,Bowl, M.R.,Bird, J.E.,Alushin, G.M.
Structural basis for tunable control of actin dynamics by myosin-15 in mechanosensory stereocilia.
Sci Adv, 8:eabl4733-eabl4733, 2022

PubMed Abstract: The motor protein myosin-15 is necessary for the development and maintenance of mechanosensory stereocilia, and mutations in myosin-15 cause hereditary deafness. In addition to transporting actin regulatory machinery to stereocilia tips, myosin-15 directly nucleates actin filament ("F-actin") assembly, which is disrupted by a progressive hearing loss mutation (p.D1647G, ""). Here, we present cryo-electron microscopy structures of myosin-15 bound to F-actin, providing a framework for interpreting the impacts of deafness mutations on motor activity and actin nucleation. Rigor myosin-15 evokes conformational changes in F-actin yet maintains flexibility in actin's D-loop, which mediates inter-subunit contacts, while the mutant locks the D-loop in a single conformation. Adenosine diphosphate-bound myosin-15 also locks the D-loop, which correspondingly blunts actin-polymerization stimulation. We propose myosin-15 enhances polymerization by bridging actin protomers, regulating nucleation efficiency by modulating actin's structural plasticity in a myosin nucleotide state-dependent manner. This tunable regulation of actin polymerization could be harnessed to precisely control stereocilium height.

PubMed: 35857845
DOI: 10.1126/sciadv.abl4733

実験手法

ELECTRON MICROSCOPY (2.83 Å)