Three-dimensional organization of troponin on cardiac muscle thin filaments in the relaxed state
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Authors
Yang, ShixinBarbu-Tudoran, Lucian
Orzechowski, Marek
Craig, Roger
Trinick, John
White, Howard
Lehman, William
UMass Chan Affiliations
Department of Cell and Developmental BiologyDocument Type
Journal ArticlePublication Date
2014-02-18
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Muscle contraction is regulated by troponin-tropomyosin, which blocks and unblocks myosin binding sites on actin. To elucidate this regulatory mechanism, the three-dimensional organization of troponin and tropomyosin on the thin filament must be determined. Although tropomyosin is well defined in electron microscopy helical reconstructions of thin filaments, troponin density is mostly lost. Here, we determined troponin organization on native relaxed cardiac muscle thin filaments by applying single particle reconstruction procedures to negatively stained specimens. Multiple reference models led to the same final structure, indicating absence of model bias in the procedure. The new reconstructions clearly showed F-actin, tropomyosin, and troponin densities. At the 25 A resolution achieved, troponin was considerably better defined than in previous reconstructions. The troponin density closely resembled the shape of troponin crystallographic structures, facilitating detailed interpretation of the electron microscopy density map. The orientation of troponin-T and the troponin core domain established troponin polarity. Density attributable to the troponin-I mobile regulatory domain was positioned where it could hold tropomyosin in its blocking position on actin, thus suggesting the underlying structural basis of thin filament regulation. Our previous understanding of thin filament regulation had been limited to known movements of tropomyosin that sterically block and unblock myosin binding sites on actin. We now show how troponin, the Ca(2+) sensor, may control these movements, ultimately determining whether muscle contracts or relaxes. reserved.Source
Yang S, Barbu-Tudoran L, Orzechowski M, Craig R, Trinick J, White H, Lehman W. Three-dimensional organization of troponin on cardiac muscle thin filaments in the relaxed state. Biophys J. 2014 Feb 18;106(4):855-64. doi:10.1016/j.bpj.2014.01.007. Link to article on publisher's siteDOI
10.1016/j.bpj.2014.01.007Permanent Link to this Item
http://hdl.handle.net/20.500.14038/27673PubMed ID
24559988Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.bpj.2014.01.007