Myosin filament 3D structure in mammalian cardiac muscle

Hind A. AL-Khayat, Edward P. Morris, Robert W. Kensler, John M. Squire

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    Abstract

    A number of cardiac myopathies (e.g. familial hypertrophic cardiomyopathy and dilated cardiomyopathy) are linked to mutations in cardiac muscle myosin filament proteins, including myosin and myosin binding protein C (MyBP-C). To understand the myopathies it is necessary to know the normal 3D structure of these filaments. We have carried out 3D single particle analysis of electron micrograph images of negatively stained isolated myosin filaments from rabbit cardiac muscle. Single filament images were aligned and divided into segments about 2 × 430 Å long, each of which was treated as an independent 'particle'. The resulting 40 Å resolution 3D reconstruction showed both axial and azimuthal (no radial) myosin head perturbations within the 430 Å repeat, with successive crown rotations of approximately 60°, 60° and 0°, rather than the regular 40° for an unperturbed helix. However, it is shown that the projecting density peaks appear to start at low radius from origins closer to those expected for an unperturbed helical filament, and that the azimuthal perturbation especially increases with radius. The head arrangements in rabbit cardiac myosin filaments are very similar to those in fish skeletal muscle myosin filaments, suggesting a possible general structural theme for myosin filaments in all vertebrate striated muscles (skeletal and cardiac).

    Original languageEnglish
    Pages (from-to)117-126
    Number of pages10
    JournalJournal of Structural Biology
    Volume163
    Issue number2
    DOIs
    Publication statusPublished - 1 Aug 2008

    Keywords

    • 3D reconstruction
    • Mammalian heart muscle
    • MyBP-C
    • Myosin filaments
    • Rabbit cardiac muscle
    • Single particle analysis

    ASJC Scopus subject areas

    • Structural Biology

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  • Cite this

    AL-Khayat, H. A., Morris, E. P., Kensler, R. W., & Squire, J. M. (2008). Myosin filament 3D structure in mammalian cardiac muscle. Journal of Structural Biology, 163(2), 117-126. https://doi.org/10.1016/j.jsb.2008.03.011