A carboxyl terminal missense mutant Arg278Cys of human cardiac troponin T that causes familial hypertrophic cardiomyopathy was expressed in Escherichia coli, purified, and exchanged into rabbit cardiac skinned muscle fibers using a troponin exchange technique. Compared to the fibers exchanged with human cardiac wild-type troponin T, the fibers exchanged with the mutant Arg278Cys developed less maximum force with a decreased cooperativity and a slightly increased Ca2+ sensitivity, resulting in a significant elevation of sub-half-maximal force. Since intact cardiac muscle is thought to never be activated beyond the half-maximum level, the results suggest that an enhanced myofilament response to Ca2+ may be responsible for the pathogenesis of hypertrophic cardiomyopathy associated with this mutation. The results also provide the first evidence that the carboxyl terminal region of cardiac troponin T plays an important role probably through its interaction with tropomyosin in allowing troponin complex to inhibit the muscle contraction at low Ca2+, in agreement with the hypothesis deduced from the previous studies on fast skeletal troponin T.
|Number of pages||4|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - Jul 22 1999|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology