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

24 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 - Aug 2008
Externally publishedYes

Fingerprint

Myosins
Myocardium
Cardiac Myosins
Muscular Diseases
Familial Hypertrophic Cardiomyopathy
Skeletal Muscle Myosins
Rabbits
Striated Muscle
Dilated Cardiomyopathy
Crowns
Vertebrates
Fishes
Head
Electrons
Mutation
Proteins

Keywords

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

ASJC Scopus subject areas

  • Structural Biology

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

Myosin filament 3D structure in mammalian cardiac muscle. / AL-Khayat, Hind A.; Morris, Edward P.; Kensler, Robert W.; Squire, John M.

In: Journal of Structural Biology, Vol. 163, No. 2, 08.2008, p. 117-126.

Research output: Contribution to journalArticle

AL-Khayat, HA, Morris, EP, Kensler, RW & Squire, JM 2008, 'Myosin filament 3D structure in mammalian cardiac muscle', Journal of Structural Biology, vol. 163, no. 2, pp. 117-126. https://doi.org/10.1016/j.jsb.2008.03.011
AL-Khayat, Hind A. ; Morris, Edward P. ; Kensler, Robert W. ; Squire, John M. / Myosin filament 3D structure in mammalian cardiac muscle. In: Journal of Structural Biology. 2008 ; Vol. 163, No. 2. pp. 117-126.
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