Three-dimensional structure of vertebrate cardiac muscle myosin filaments

@article{citeulike:2410571, abstract = {Contraction of the heart results from interaction of the myosin and actin filaments. Cardiac myosin filaments consist of the molecular motor myosin II, the sarcomeric template protein, titin, and the cardiac modulatory protein, myosin binding protein C (MyBP-C). Inherited hypertrophic cardiomyopathy (HCM) is a disease caused mainly by mutations in these proteins. The structure of cardiac myosin filaments and the alterations caused by HCM mutations are unknown. We have used electron microscopy and image analysis to determine the three-dimensional structure of myosin filaments from wild-type mouse cardiac muscle and from a MyBP-C knockout model for HCM. Three-dimensional reconstruction of the wild-type filament reveals the conformation of the myosin heads and the organization of titin and MyBP-C at 4 nm resolution. Myosin heads appear to interact with each other intramolecularly, as in off-state smooth muscle myosin [Wendt T, Taylor D, Trybus KM, Taylor K (2001) Proc Natl Acad Sci USA 98:43614366], suggesting that all relaxed muscle myosin IIs may adopt this conformation. Titin domains run in an elongated strand along the filament surface, where they appear to interact with part of MyBP-C and with the myosin backbone. In the knockout filament, some of the myosin head interactions are disrupted, suggesting that MyBP-C is important for normal relaxation of the filament. These observations provide key insights into the role of the myosin filament in cardiac contraction, assembly, and disease. The techniques we have developed should be useful in studying the structural basis of other myosin-related HCM diseases. 10.1073/pnas.0708912105}, author = {Zoghbi, Maria E. and Woodhead, John L. and Moss, Richard L. and Craig, Roger }, citeulike-article-id = {2410571}, doi = {10.1073/pnas.0708912105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {em, motor, mutant, myosin, structure}, month = {February}, number = {7}, pages = {2386--2390}, posted-at = {2008-02-22 09:22:19}, priority = {2}, title = {Three-dimensional structure of vertebrate cardiac muscle myosin filaments}, url = {http://dx.doi.org/10.1073/pnas.0708912105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2410571 L3 - citeulike-article-id:2410571 TI - Three-dimensional structure of vertebrate cardiac muscle myosin filaments JF - Proceedings of the National Academy of Sciences VL - 105 IS - 7 SP - 2386 EP - 2390 N2 - Contraction of the heart results from interaction of the myosin and actin filaments. Cardiac myosin filaments consist of the molecular motor myosin II, the sarcomeric template protein, titin, and the cardiac modulatory protein, myosin binding protein C (MyBP-C). Inherited hypertrophic cardiomyopathy (HCM) is a disease caused mainly by mutations in these proteins. The structure of cardiac myosin filaments and the alterations caused by HCM mutations are unknown. We have used electron microscopy and image analysis to determine the three-dimensional structure of myosin filaments from wild-type mouse cardiac muscle and from a MyBP-C knockout model for HCM. Three-dimensional reconstruction of the wild-type filament reveals the conformation of the myosin heads and the organization of titin and MyBP-C at 4 nm resolution. Myosin heads appear to interact with each other intramolecularly, as in off-state smooth muscle myosin [Wendt T, Taylor D, Trybus KM, Taylor K (2001) Proc Natl Acad Sci USA 98:43614366], suggesting that all relaxed muscle myosin IIs may adopt this conformation. Titin domains run in an elongated strand along the filament surface, where they appear to interact with part of MyBP-C and with the myosin backbone. In the knockout filament, some of the myosin head interactions are disrupted, suggesting that MyBP-C is important for normal relaxation of the filament. These observations provide key insights into the role of the myosin filament in cardiac contraction, assembly, and disease. The techniques we have developed should be useful in studying the structural basis of other myosin-related HCM diseases. 10.1073/pnas.0708912105 KW - em KW - motor KW - mutant KW - myosin KW - structure AU - Zoghbi, Maria AU - Woodhead, John AU - Moss, Richard AU - Craig, Roger PY - 2008/02/19/ UR - http://dx.doi.org/10.1073/pnas.0708912105 ER -