Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy

Fumiaki Yumoto, Qun Wei Lu, Sachio Morimoto, Hiroyuki Tanaka, Naoko Kono, Koji Nagata, Takao Ojima, Fumi Takahashi, Yoshikazu Miwa, Toshiyuki Sasaguri, Kiyoyoshi Nishita, Masaru Tanokura, Iwao Ohtsuki

研究成果: ジャーナルへの寄稿記事

58 引用 (Scopus)

抄録

Six missense mutations in human cardiac troponin I (cTnI) were recently found to cause restrictive cardiomyopathy (RCM). We have bacterially expressed and purified these human cTnI mutants and examined their functional and structural consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed that these mutations had much greater Ca2+-sensitizing effects on force generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The mutation K178E in the second actin-tropomyosin (Tm) binding region showed a particularly potent Ca2+-sensitizing effect among the six RCM-causing mutations. Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this mutation does not extensively affect the structure of the whole cTnI molecule, but induces an unexpectedly subtle change in the structure of a region around the mutated residue. The results indicate that the K178E mutation has a localized effect on a structure that is critical to the regulatory function of the second actin-Tm binding region of cTnI. The present study also suggests that both HCM and RCM involving cTnI mutations share a common feature of increased Ca2+ sensitivity of cardiac myofilament, but more severe change in Ca2+ sensitivity is associated with the clinical phenotype of RCM.

元の言語英語
ページ(範囲)1519-1526
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
338
発行部数3
DOI
出版物ステータス出版済み - 12 23 2005

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Restrictive Cardiomyopathy
Troponin I
Myofibrils
Mutation
Tropomyosin
Hypertrophic Cardiomyopathy
Actins
Missense Mutation
Circular Dichroism
Nuclear magnetic resonance spectroscopy
Muscle
Myocardium
Magnetic Resonance Spectroscopy
Phenotype
Molecules
Fibers

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy. / Yumoto, Fumiaki; Lu, Qun Wei; Morimoto, Sachio; Tanaka, Hiroyuki; Kono, Naoko; Nagata, Koji; Ojima, Takao; Takahashi, Fumi; Miwa, Yoshikazu; Sasaguri, Toshiyuki; Nishita, Kiyoyoshi; Tanokura, Masaru; Ohtsuki, Iwao.

:: Biochemical and Biophysical Research Communications, 巻 338, 番号 3, 23.12.2005, p. 1519-1526.

研究成果: ジャーナルへの寄稿記事

Yumoto, F, Lu, QW, Morimoto, S, Tanaka, H, Kono, N, Nagata, K, Ojima, T, Takahashi, F, Miwa, Y, Sasaguri, T, Nishita, K, Tanokura, M & Ohtsuki, I 2005, 'Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy', Biochemical and Biophysical Research Communications, 巻. 338, 番号 3, pp. 1519-1526. https://doi.org/10.1016/j.bbrc.2005.10.116
Yumoto, Fumiaki ; Lu, Qun Wei ; Morimoto, Sachio ; Tanaka, Hiroyuki ; Kono, Naoko ; Nagata, Koji ; Ojima, Takao ; Takahashi, Fumi ; Miwa, Yoshikazu ; Sasaguri, Toshiyuki ; Nishita, Kiyoyoshi ; Tanokura, Masaru ; Ohtsuki, Iwao. / Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy. :: Biochemical and Biophysical Research Communications. 2005 ; 巻 338, 番号 3. pp. 1519-1526.
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abstract = "Six missense mutations in human cardiac troponin I (cTnI) were recently found to cause restrictive cardiomyopathy (RCM). We have bacterially expressed and purified these human cTnI mutants and examined their functional and structural consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed that these mutations had much greater Ca2+-sensitizing effects on force generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The mutation K178E in the second actin-tropomyosin (Tm) binding region showed a particularly potent Ca2+-sensitizing effect among the six RCM-causing mutations. Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this mutation does not extensively affect the structure of the whole cTnI molecule, but induces an unexpectedly subtle change in the structure of a region around the mutated residue. The results indicate that the K178E mutation has a localized effect on a structure that is critical to the regulatory function of the second actin-Tm binding region of cTnI. The present study also suggests that both HCM and RCM involving cTnI mutations share a common feature of increased Ca2+ sensitivity of cardiac myofilament, but more severe change in Ca2+ sensitivity is associated with the clinical phenotype of RCM.",
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AU - Tanaka, Hiroyuki

AU - Kono, Naoko

AU - Nagata, Koji

AU - Ojima, Takao

AU - Takahashi, Fumi

AU - Miwa, Yoshikazu

AU - Sasaguri, Toshiyuki

AU - Nishita, Kiyoyoshi

AU - Tanokura, Masaru

AU - Ohtsuki, Iwao

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