Orientation of myosin binding protein C in the cardiac muscle sarcomere determined by domain-specific immuno-EM
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UMass Chan Affiliations
Department of Cell and Developmental BiologyDocument Type
Journal ArticlePublication Date
2015-01-30Keywords
AnimalsCarrier Proteins
Image Processing, Computer-Assisted
Mice
Microscopy, Fluorescence
Microscopy, Immunoelectron
Myocardial Contraction
Myocardium
Protein Isoforms
Sarcomeres
cMyBP-C
cardiac muscle contraction
cardiac muscle disease
cardiac muscle regulation
cardiac muscle structure
Cell and Developmental Biology
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
Metadata
Show full item recordAbstract
Myosin binding protein C is a thick filament protein of vertebrate striated muscle. The cardiac isoform [cardiac myosin binding protein C (cMyBP-C)] is essential for normal cardiac function, and mutations in cMyBP-C cause cardiac muscle disease. The rod-shaped molecule is composed primarily of 11 immunoglobulin- or fibronectin-like domains and is located at nine sites, 43nm apart, in each half of the A-band. To understand how cMyBP-C functions, it is important to know its structural organization in the sarcomere, as this will affect its ability to interact with other sarcomeric proteins. Several models, in which cMyBP-C wraps around, extends radially from, or runs axially along the thick filament, have been proposed. Our goal was to define cMyBP-C orientation by determining the relative axial positions of different cMyBP-C domains. Immuno-electron microscopy was performed using mouse cardiac myofibrils labeled with antibodies specific to the N- and C-terminal domains and to the middle of cMyBP-C. Antibodies to all regions of the molecule, except the C-terminus, labeled at the same nine axial positions in each half A-band, consistent with a circumferential and/or radial rather than an axial orientation of the bulk of the molecule. The C-terminal antibody stripes were slightly displaced axially, demonstrating an axial orientation of the C-terminal three domains, with the C-terminus closer to the M-line. These results, combined with previous studies, suggest that the C-terminal domains of cMyBP-C run along the thick filament surface, while the N-terminus extends toward neighboring thin filaments. This organization provides a structural framework for understanding cMyBP-C's modulation of cardiac muscle contraction.Source
J Mol Biol. 2015 Jan 30;427(2):274-86. doi: 10.1016/j.jmb.2014.10.023. Link to article on publisher's site.DOI
10.1016/j.jmb.2014.10.023Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26454PubMed ID
25451032Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.jmb.2014.10.023
Scopus Count
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