Oral Presentation 2014 International Biophysics Congress

Does the super-relaxed state of myosin exist in the human heart? (#220)

James McNamara 1 , Amy Li 1 , Peter MacDonald 2 , Cris dos Remedios 1 , Arthur Cooke 3
  1. Department of Anatomy and Histology, The University of Sydney, Sydney, NSW, Australia
  2. Cardiopulmonary Transplant Unit, St Vincent’s Hospital, Darlinghurst, NSW, Australia
  3. Department of Biochemistry & Biophysics, University of California, San Francisco, CA, USA

The super-relaxed state (SRX) of the motor protein myosin was only recently discovered [1]. In the sarcomere it exists as a population of myosin heads that are close to the surface of the thick filaments rather than projecting from their surface. SRX myosin has a much lower ATPase activity than purified myosin but this inhibited state can be activated [2]. SRX may be involved in slow processes such as the turnover of damaged or denatured myosin filaments. It may also provide cardioprotection during times of stress or hypoxia. SRX myosin has been reported for both skeletal and cardiac myosins in rabbits [3], but this is the first time it has been demonstrated in human cardiac tissue. Thus, it may be possible to convert SRX myosin into active myosin as a treatment for patients with heart failure. Using very small samples of left ventricle tissue from heart transplant patients we will examine whether the population of SRX myosin changes in heart failure and also whether it changes as a function of age.

  1. Stewart, M. A., Franks-Skiba, K., Chen, S., & Cooke, R. (2010). Myosin ATP turnover rate is a mechanism involved in thermogenesis in resting skeletal muscle fibers. Proc Natl Acad Sci U S A, 107(1), 430-435.
  2. Cooke, R. (2011). The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle. Biophys Rev, 3(1), 33-45.
  3. Hooijman, P., Stewart, Melanie A., & Cooke, R. (2011). A New State of Cardiac Myosin with Very Slow ATP Turnover: A Potential Cardioprotective Mechanism in the Heart. Biophys J, 100(8), 1969-1976.