RGD Reference Report - Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy. - Rat Genome Database

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

Authors: Yumoto, F  Lu, QW  Morimoto, S  Tanaka, H  Kono, N  Nagata, K  Ojima, T  Takahashi-Yanaga, F  Miwa, Y  Sasaguri, T  Nishita, K  Tanokura, M  Ohtsuki, I 
Citation: Yumoto F, etal., Biochem Biophys Res Commun. 2005 Dec 23;338(3):1519-26. Epub 2005 Nov 2.
RGD ID: 1580419
Pubmed: PMID:16288990   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2005.10.116   (Journal Full-text)

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.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
TNNI3Humanrestrictive cardiomyopathy  IAGP  RGD 
Tnni3Ratrestrictive cardiomyopathy  ISOTNNI3 (Homo sapiens) RGD 
Tnni3Mouserestrictive cardiomyopathy  ISOTNNI3 (Homo sapiens) RGD 


Genes (Rattus norvegicus)
Tnni3  (troponin I3, cardiac type)

Genes (Mus musculus)
Tnni3  (troponin I, cardiac 3)

Genes (Homo sapiens)
TNNI3  (troponin I3, cardiac type)