8q6t
Helical reconstruction of the relaxed thick filament from FIB milled left ventricular mouse myofibrils
Structural highlights
FunctionMYH7_MOUSE Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle.[UniProtKB:P12883] Publication Abstract from PubMedThe thick filament is a key component of sarcomeres, the basic units of striated muscle(1). Alterations in thick filament proteins are associated with familial hypertrophic cardiomyopathy and other heart and muscle diseases(2). Despite the central importance of the thick filament, its molecular organization remains unclear. Here we present the molecular architecture of native cardiac sarcomeres in the relaxed state, determined by cryo-electron tomography. Our reconstruction of the thick filament reveals the three-dimensional organization of myosin, titin and myosin-binding protein C (MyBP-C). The arrangement of myosin molecules is dependent on their position along the filament, suggesting specialized capacities in terms of strain susceptibility and force generation. Three pairs of titin-alpha and titin-beta chains run axially along the filament, intertwining with myosin tails and probably orchestrating the length-dependent activation of the sarcomere. Notably, whereas the three titin-alpha chains run along the entire length of the thick filament, titin-beta chains do not. The structure also demonstrates that MyBP-C bridges thin and thick filaments, with its carboxy-terminal region binding to the myosin tails and directly stabilizing the OFF state of the myosin heads in an unforeseen manner. These results provide a foundation for future research investigating muscle disorders involving sarcomeric components. Structure of the native myosin filament in the relaxed cardiac sarcomere.,Tamborrini D, Wang Z, Wagner T, Tacke S, Stabrin M, Grange M, Kho AL, Rees M, Bennett P, Gautel M, Raunser S Nature. 2023 Nov;623(7988):863-871. doi: 10.1038/s41586-023-06690-5. Epub 2023 , Nov 1. PMID:37914933[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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