Functional consequences of the deletion mutation ΔGlu160 in human cardiac troponin T

Keita Harada, Fumi Takahashi, Reiko Minakami, Sachio Morimoto, Iwao Ohtsuki

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

To explore the functional consequences of a deletion mutation of troponin T (ΔGlu160) found in familial hypertrophic cardiomyopathy, the mutant human cardiac troponin T, and wild-type troponins T, I, and C were expressed in Escherichia coli and directly incorporated into isolated porcine cardiac myofibrils using our previously reported troponin exchange technique. The mutant troponin T showed a slightly reduced potency in replacing the endogenous troponin complex in myofibrils and did not affect the inhibitory action of troponin I but potentiated the neutralizing action of troponin C, suggesting that the deletion of a single amino acid, Glu-160, in the strong tropomyosin-binding region affects the tropomyosin binding affinity of the entire troponin T molecule and alters the interaction between troponin I and troponin C within ternary troponin complex in the thin filament. This mutation also increased the Ca2+ sensitivity of the myofibrillar ATPase activity, as in the case of other mutations in troponin T with clinical phenotypes of poor prognosis similar to that of ΔGlu160. These results provide strong evidence that the increased Ca2+ sensitivity of cardiac myofilament is a typical functional consequence of the troponin T mutation associated with a malignant form of hypertrophic cardiomyopathy.

Original languageEnglish
Pages (from-to)263-268
Number of pages6
JournalJournal of Biochemistry
Volume127
Issue number2
DOIs
Publication statusPublished - Jan 1 2000

Fingerprint

Troponin T
Sequence Deletion
Troponin C
Troponin
Troponin I
Myofibrils
Tropomyosin
Mutation
Familial Hypertrophic Cardiomyopathy
Hypertrophic Cardiomyopathy
Escherichia coli
Adenosine Triphosphatases
Swine
Phenotype
Amino Acids
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Functional consequences of the deletion mutation ΔGlu160 in human cardiac troponin T. / Harada, Keita; Takahashi, Fumi; Minakami, Reiko; Morimoto, Sachio; Ohtsuki, Iwao.

In: Journal of Biochemistry, Vol. 127, No. 2, 01.01.2000, p. 263-268.

Research output: Contribution to journalArticle

Harada, Keita ; Takahashi, Fumi ; Minakami, Reiko ; Morimoto, Sachio ; Ohtsuki, Iwao. / Functional consequences of the deletion mutation ΔGlu160 in human cardiac troponin T. In: Journal of Biochemistry. 2000 ; Vol. 127, No. 2. pp. 263-268.
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