Mutations in Troponin I (Tnl) and Troponin T (TnT) are closely linked to familial hypertrophic cardiomyo-pathy (FHC) and hypertrophic cardiomyopathy (HCM), but the underlying molecular mechanism is not yet well understood. There might be a close link between the defective dynamic properties and the functional aberrations of hcTroponin. To prove this hypothesis, we undertook detailed NMR relaxation measurements of [2H, 13C, 15N] labeled proteins reconstituted into hcTroponin in both the Ca2+- and the Mg2+-loaded state. The wild-type Tnl and two FHC causing mutations, TnI(G203S) and TnI(AK183), were investigated. To ensure that defective dynamic properties are not only a particular feature for mutations in the flexible part of Tnl, measurements of the TnT mutation TnT(R278P) were also performed. For all mutations significant dynamic changes in the area for Troponin C (TnC) and actin-Tm binding were obtained. These measurements provide important information to understand the functional aberrations of FHC and HCM causing mutation in human cardiac Troponin (hcTn).
CITATION STYLE
Lassalle, M. W. (2010). Defective dynamic properties of human cardiac troponin mutations. Bioscience, Biotechnology and Biochemistry, 74(1), 82–91. https://doi.org/10.1271/bbb.90586
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