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

Sachio Morimoto, Hiroyuki Nakaura, Fumi Yanaga, Iwao Ohtsuki

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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
Volume261
Issue number1
DOIs
Publication statusPublished - Jul 22 1999

Fingerprint

Troponin T
Missense Mutation
Muscle
Troponin
Fibers
Myocardium
Familial Hypertrophic Cardiomyopathy
Tropomyosin
Myofibrils
Hypertrophic Cardiomyopathy
Muscle Contraction
Escherichia coli
Rabbits
Mutation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Functional consequences of a carboxyl terminal missense mutation Arg278Cys in human cardiac troponin T. / Morimoto, Sachio; Nakaura, Hiroyuki; Yanaga, Fumi; Ohtsuki, Iwao.

In: Biochemical and Biophysical Research Communications, Vol. 261, No. 1, 22.07.1999, p. 79-82.

Research output: Contribution to journalArticle

Morimoto, Sachio ; Nakaura, Hiroyuki ; Yanaga, Fumi ; Ohtsuki, Iwao. / Functional consequences of a carboxyl terminal missense mutation Arg278Cys in human cardiac troponin T. In: Biochemical and Biophysical Research Communications. 1999 ; Vol. 261, No. 1. pp. 79-82.
@article{ad095c9bbdbf4388b94500ecd12ea8f8,
title = "Functional consequences of a carboxyl terminal missense mutation Arg278Cys in human cardiac troponin T",
abstract = "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.",
author = "Sachio Morimoto and Hiroyuki Nakaura and Fumi Yanaga and Iwao Ohtsuki",
year = "1999",
month = "7",
day = "22",
doi = "10.1006/bbrc.1999.1000",
language = "English",
volume = "261",
pages = "79--82",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Functional consequences of a carboxyl terminal missense mutation Arg278Cys in human cardiac troponin T

AU - Morimoto, Sachio

AU - Nakaura, Hiroyuki

AU - Yanaga, Fumi

AU - Ohtsuki, Iwao

PY - 1999/7/22

Y1 - 1999/7/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033595110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033595110&partnerID=8YFLogxK

U2 - 10.1006/bbrc.1999.1000

DO - 10.1006/bbrc.1999.1000

M3 - Article

VL - 261

SP - 79

EP - 82

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -