Cardiac Myosin / Myosin / Human / folded-back off state / CONTRACTILE PROTEIN
機能・相同性
機能・相同性情報
myosin II heavy chain binding / muscle cell fate specification / regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / A band / regulation of striated muscle contraction / cardiac myofibril / muscle myosin complex / cardiac myofibril assembly / regulation of the force of heart contraction ...myosin II heavy chain binding / muscle cell fate specification / regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / A band / regulation of striated muscle contraction / cardiac myofibril / muscle myosin complex / cardiac myofibril assembly / regulation of the force of heart contraction / transition between fast and slow fiber / myosin filament / positive regulation of ATP-dependent activity / adult heart development / Striated Muscle Contraction / cardiac muscle hypertrophy in response to stress / muscle filament sliding / myosin complex / myosin II complex / I band / structural constituent of muscle / ventricular cardiac muscle tissue morphogenesis / microfilament motor activity / myosin heavy chain binding / heart contraction / positive regulation of the force of heart contraction / myofibril / cytoskeletal motor activity / actin monomer binding / skeletal muscle contraction / striated muscle contraction / ATP metabolic process / skeletal muscle tissue development / stress fiber / cardiac muscle contraction / muscle contraction / regulation of heart rate / sarcomere / post-embryonic development / negative regulation of cell growth / Z disc / actin filament binding / heart development / calmodulin binding / cytoskeleton / calcium ion binding / ATP binding / cytosol / cytoplasm 類似検索 - 分子機能
: / DNA repair protein XRCC4-like, C-terminal / Myosin tail / Myosin tail / Myosin N-terminal SH3-like domain / Myosin S1 fragment, N-terminal / Myosin, N-terminal, SH3-like / Myosin N-terminal SH3-like domain profile. / Short calmodulin-binding motif containing conserved Ile and Gln residues. / IQ motif, EF-hand binding site ...: / DNA repair protein XRCC4-like, C-terminal / Myosin tail / Myosin tail / Myosin N-terminal SH3-like domain / Myosin S1 fragment, N-terminal / Myosin, N-terminal, SH3-like / Myosin N-terminal SH3-like domain profile. / Short calmodulin-binding motif containing conserved Ile and Gln residues. / IQ motif, EF-hand binding site / Myosin head, motor domain / Myosin head (motor domain) / Myosin motor domain profile. / Myosin. Large ATPases. / IQ motif profile. / Kinesin motor domain superfamily / : / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / EF-hand domain pair / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
NIH-RM1GM131981-01
米国
Agence Nationale de la Recherche (ANR)
ANR-21-CE11-0022-01
フランス
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
NIH-R01GM33289
米国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Cryo-EM structure of the folded-back state of human β-cardiac myosin. 著者: Alessandro Grinzato / Daniel Auguin / Carlos Kikuti / Neha Nandwani / Dihia Moussaoui / Divya Pathak / Eaazhisai Kandiah / Kathleen M Ruppel / James A Spudich / Anne Houdusse / Julien Robert-Paganin / 要旨: To save energy and precisely regulate cardiac contractility, cardiac muscle myosin heads are sequestered in an 'off' state that can be converted to an 'on' state when exertion is increased. The 'off' ...To save energy and precisely regulate cardiac contractility, cardiac muscle myosin heads are sequestered in an 'off' state that can be converted to an 'on' state when exertion is increased. The 'off' state is equated with a folded-back structure known as the interacting-heads motif (IHM), which is a regulatory feature of all class-2 muscle and non-muscle myosins. We report here the human β-cardiac myosin IHM structure determined by cryo-electron microscopy to 3.6 Å resolution, providing details of all the interfaces stabilizing the 'off' state. The structure shows that these interfaces are hot spots of hypertrophic cardiomyopathy mutations that are thought to cause hypercontractility by destabilizing the 'off' state. Importantly, the cardiac and smooth muscle myosin IHM structures dramatically differ, providing structural evidence for the divergent physiological regulation of these muscle types. The cardiac IHM structure will facilitate development of clinically useful new molecules that modulate IHM stability.
モデルのタイプ: OTHER 詳細: The coiled-coil S2 region was fitted from the crystal structure (Blankenfeldt et al., 2006; PDB code 2FXM). The IQ2/RLC region was obtained by homology modeling based on the SmMyo2 IHM ...詳細: The coiled-coil S2 region was fitted from the crystal structure (Blankenfeldt et al., 2006; PDB code 2FXM). The IQ2/RLC region was obtained by homology modeling based on the SmMyo2 IHM (Heissler et al., 2021; PDB code 7MF3).
最終 再構成
解像度のタイプ: BY AUTHOR / 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 213596