Functional consequences of a carboxyl terminal missense mutation Arg278Cys in human cardiac troponin T

Sachio Morimoto, Hiroyuki Nakaura, Fumi Yanaga, Iwao Ohtsuki

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37 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)79-82
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - Jul 22 1999

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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