[ Back to EurekAlert! ] Public release date: 8-Nov-2007
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Contact: Andrea Moser
amoser@burnham.org
858-646-3146
Sanford-Burnham Medical Research Institute

The structural basis of familial hypertrophic cardiomyopathy is revealed

Familial Hypertrophic Cardiomyopathy (FHC), the leading cause of sudden death in athletes and young people, is a genetic disorder of the heart that is characterized by an increased thickness in tissue of the left ventricle. FHC is thought to be caused by a mutation in the myosin heavy chain, one of the components of muscle cells in the heart, which causes a disruption in the normal alignment of muscle cells otherwise known as myocardial disarray. One of the deadliest forms of FHC is caused by the R403Q mutation, which kills 50% of those affected individuals by 40 years of age. A study conducted by scientists at the Burnham Institute for Medical Research (Burnham Institute) in La Jolla, CA provides new structural evidence that the disarray at the molecular level caused by the R403Q point mutation in myosin is linked to the characteristic misalignment of muscle cells in FHC.

In a recent publication by PloS ONE, the scientific group, led by Dr. Dorit Hanein (Burnham Institute), used smooth muscle myosin to investigate the structural effects of the R403Q mutation. The group concluded that this point mutation severely disrupts actin-myosin interactions as compared to those in wildtype myosin. While myosin normally attaches to the actin filament at a fixed angle, the mutated myosin displayed a wide variety of angles at the attachment sites, thus demonstrating a structural basis for the change in function of the mutant myosin. Dr. Hanein illustrates how the conformational instability within the sarcomere affects ability of the heart to function properly and may lead to compensatory hypertrophy in cardiac muscle tissue, which is a trademark phenotype of FHC. This study allows for a better understanding of the origination of FHC at the molecular level, which may open doors for the development of drugs to treat this disorder in the future.

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Dr. Dorit Hanein is an Associate Professor within the Infectious Diseases Program at the Burnham Institute for Medical Research. The study was conducted in collaboration with the University of Vermont Department of Molecular Physiology and Biophysics.

To review the PLos ONE article, please visit http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001123.

Burnham Institute for Medical Research conducts world-class collaborative research dedicated to finding cures for human disease, improving quality of life, and thus creating a legacy for its employees, partners, donors, and community. The La Jolla, California campus was established as a nonprofit, public benefit corporation in 1976 and is now home to three major centers: a National Cancer Institute-designated Cancer Center, the Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, and the Infectious and Inflammatory Disease Center. Burnham today employs nearly 800 people, ranks consistently among the world’s top 20 organizations for the impact of its research publications, and rates fourth among all research institutes in the United States for obtaining grant funds from the National Institutes of Health. In 2006, Burnham established a center for vascular mapping and bionanotechnology in Santa Barbara, California. Burnham is also establishing a campus at Lake Nona in Orlando, Florida that will focus on diabetes and obesity research and will expand the Institute’s drug discovery capabilities, employing over 300 people. For additional information about Burnham and to learn about ways to support its research, visit www.burnham.org.



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