Affiliation:
1. Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA
2. Department of Pediatrics (Cardiology), Stanford University School of Medicine, Stanford, CA 94305, USA
Abstract
ABSTRACT
Hypertrophic cardiomyopathy is the most frequently occurring inherited cardiovascular disease, with a prevalence of more than one in 500 individuals worldwide. Genetically acquired dilated cardiomyopathy is a related disease that is less prevalent. Both are caused by mutations in the genes encoding the fundamental force-generating protein machinery of the cardiac muscle sarcomere, including human β-cardiac myosin, the motor protein that powers ventricular contraction. Despite numerous studies, most performed with non-human or non-cardiac myosin, there is no clear consensus about the mechanism of action of these mutations on the function of human β-cardiac myosin. We are using a recombinantly expressed human β-cardiac myosin motor domain along with conventional and new methodologies to characterize the forces and velocities of the mutant myosins compared with wild type. Our studies are extending beyond myosin interactions with pure actin filaments to include the interaction of myosin with regulated actin filaments containing tropomyosin and troponin, the roles of regulatory light chain phosphorylation on the functions of the system, and the possible roles of myosin binding protein-C and titin, important regulatory components of both cardiac and skeletal muscles.
Funder
Office of Extramural Research, National Institutes of Health
National Institutes of Health
National Institutes of Health Cellular, Biochemical, and Molecular Sciences Training Grant
Stanford Interdisciplinary Graduate Fellowship
Stanford Dean's Postdoctoral Fellowship
National Science Foundation Graduate Research Fellowship Program
Lucile Packard child health research institute postdoctoral grant
Publisher
The Company of Biologists
Subject
Insect Science,Molecular Biology,Animal Science and Zoology,Aquatic Science,Physiology,Ecology, Evolution, Behavior and Systematics
Cited by
59 articles.
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