title: The effect of the dilated cardiomyopathy-causing mutation Glu54Lys of alpha-tropomyosin on actin-myosin interactions during the ATPase cycle.
abstract: In order to understand how the Glu54Lys mutation of alpha-tropomyosin affects actomyosin interactions, we labeled SH1 helix of myosin subfragment-1 (S1) and the actin subdomain-1 with fluorescent probes. These proteins were incorporated into ghost muscle fibers and their conformational states were monitored during the ATPase cycle by measuring polarized fluorescence. The addition of wild-type alpha-tropomyosin to actin filaments increases the amplitude of the SH1 helix and subdomain-1 movements during the ATPase cycle, indicating the enhancement of the efficiency of work of each cross-bridge. The Glu54Lys mutation inhibits this effect. The Glu54Lys mutation also results in the coupling of the weak-binding sub-state of S1 to the strong-binding sub-state of actin thus altering the concerted conformational changes during the ATPase cycle. We suggest that these alterations will result in reduced force production, which is likely to underlie at least in part the contractile deficit observed in human dilated cardiomyopathy.
authors: Laboratory of Mechanisms of Cell Motility, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia. boroviko@mail.cytspb.rssi.ru
authors: Yurii S
authors: YS
authors: Borovikov
authors: Olga E
authors: OE
authors: Karpicheva
authors: Stanislava V
authors: SV
authors: Avrova
authors: Paul
authors: P
authors: Robinson
authors: Charles S
authors: CS
authors: Redwood
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D002311:Cardiomyopathy, Dilated; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000737:chemistry* / Q000378:metabolism; D020125:Mutation, Missense; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D014335:Tropomyosin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C490775:TPM1 protein, human; D014335:Tropomyosin; D000251:Adenosine Triphosphatases