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-Structure paper
タイトル | Cryo-EM structure of the folded-back state of human β-cardiac myosin. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 3166, Year 2023 |
掲載日 | 2023年5月31日 |
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 / |
PubMed 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. |
リンク | Nat Commun / PubMed:37258552 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.6 Å |
構造データ | EMDB-15353, PDB-8act: EMDB-15354: IHMof beta-cardiac myosin heads region |
化合物 | ChemComp-ADP: ChemComp-PO4: ChemComp-MG: |
由来 |
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キーワード | CONTRACTILE PROTEIN / Cardiac Myosin / Myosin / Human / folded-back off state |