title: [Abnormal tropomyosin function in ATPase cycle in hypertrophic and dilated cardiomyopathies].
abstract: Pathogenesis of most myopathies including inherited hypertrophic (HCM) and dilated (DCM) cardiomyopathies is based on modification of structural state of contractile proteins induced by point mutations, such as mutations in alpha-tropomyosin (TM). To understand the mechanism of abnormal function of contractile system of muscle fiber due to Glu180Gly, Asp175 or Glu40Lys, Glu54Lys mutations in alpha-TM associated with HCM or DCM, we specifically labeled alpha-TM by fluorescence probe 5-IAF after Cys-190 and examined the position and mobility of the IAF-TM in the ATP hydrolysis cycle using polarized fluorescence technique. Analysis of the data suggested that the point mutations in alpha-TM associated with hypertrophic or dilated cardiomyopathy caused abnormal changes in the affinity ofTM to actin and in the position of this protein on the thin filaments in the ATPase cycle. Mutations in alpha-TM associated with HCM caused a shift of TM strands to the center of the thin filament and increased a range of tropomyosin motion and affinity of this protein to actin in the ATPase cycle. In contrast, mutations in alpha-TM associated with DCM shifted the protein to the periphery of the thin filament, reduced the amplitude of the TM movement and its affinity for actin. It is proposed that anomalous behavior of TM on the thin filaments in ATPase cycle may provoke the dysfunction of the cardiac muscle in patients with HCM and DCM.
authors: Iu S
authors: IuS
authors: Borovikov
authors: O E
authors: OE
authors: Karpicheva
authors: N A
authors: NA
authors: Rysev
authors: C S
authors: CS
authors: Redwood
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism / Q000503:physiopathology; D005452:Fluoresceins; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D006801:Humans; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; C490775:TPM1 protein, human; D014335:Tropomyosin; C015296:5-iodoacetamidofluorescein; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases