[HTML][HTML] Heterologous expression of a cardiomyopathic myosin that is defective in its actin interaction.
HL Sweeney, AJ Straceski, LA Leinwand… - Journal of Biological …, 1994 - Elsevier
HL Sweeney, AJ Straceski, LA Leinwand, BA Tikunov, L Faust
Journal of Biological Chemistry, 1994•ElsevierA point mutation in the heavy chain of cardiac myosin, resulting in replacement of an
arginine (Arg) with glutamine (Gln), has been linked to hypertrophic cardiomyopathy in
humans (Geisterfer-Lowrance, AAT, Kass, S., Tanigawa, G., Vosberg, H.-P., McKenna, W.,
Seidman, JG, and Seidman, CE (1990) Cell 62, 999-1006). To determine the functional
impact of this mutation, baculovirus-driven coexpression of myosin heavy and light chains
has been developed. The Arg-403–> Gln mutation resulted in cardiac myosin with normal …
arginine (Arg) with glutamine (Gln), has been linked to hypertrophic cardiomyopathy in
humans (Geisterfer-Lowrance, AAT, Kass, S., Tanigawa, G., Vosberg, H.-P., McKenna, W.,
Seidman, JG, and Seidman, CE (1990) Cell 62, 999-1006). To determine the functional
impact of this mutation, baculovirus-driven coexpression of myosin heavy and light chains
has been developed. The Arg-403–> Gln mutation resulted in cardiac myosin with normal …
A point mutation in the heavy chain of cardiac myosin, resulting in replacement of an arginine (Arg) with glutamine (Gln), has been linked to hypertrophic cardiomyopathy in humans (Geisterfer-Lowrance, A. A. T., Kass, S., Tanigawa, G., Vosberg, H.-P., McKenna, W., Seidman, J. G., and Seidman, C. E. (1990) Cell 62, 999-1006). To determine the functional impact of this mutation, baculovirus-driven coexpression of myosin heavy and light chains has been developed. The Arg-403–>Gln mutation resulted in cardiac myosin with normal ATPase activity in the absence of actin. However, in the presence of actin, ATPase activity was greatly reduced (Vmax decreased > 3.5-fold and K(app) increased > 3-fold). In vitro motility was reduced nearly 5-fold by this single amino acid mutation. Thus, Arg-403 likely contributes to an important interaction at the actin interface of myosin. Replacement of Arg-403 with Gln leads to decreased rate(s) of transition within the actin-myosin crossbridge cycle. In humans, this mutation will result in decreased power output per unit area of cardiac muscle, likely providing a stimulus for hypertrophy.
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