title: Aberrant movement of β-tropomyosin associated with congenital myopathy causes defective response of myosin heads and actin during the ATPase cycle.
abstract: We have investigated the effect of the E41K, R91G, and E139del β-tropomyosin (TM) mutations that cause congenital myopathy on the position of TM and orientation of actin monomers and myosin heads at different mimicked stages of the ATPase cycle in troponin-free ghost muscle fibers by polarized fluorimetry. A multi-step shifting of wild-type TM to the filament center accompanied by an increase in the amount of switched on actin monomers and the strongly bound myosin heads was observed during the ATPase cycle. The R91G mutation shifts TM further towards the inner and outer domains of actin at the strong- and weak-binding stages, respectively. The E139del mutation retains TM near the inner domains, while the E41K mutation captures it near the outer domains. The E41K and R91G mutations can induce the strong binding of myosin heads to actin, when TM is located near the outer domains. The E139del mutation inhibits the amount of strongly bound myosin heads throughout the ATPase cycle.
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia. Electronic address: borovikov@incras.ru.
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Borovikov
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia.
authors.forename: Stanislava V
authors.initials: SV
authors.lastname: Avrova
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia.
authors.forename: Nikita A
authors.initials: NA
authors.lastname: Rysev
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Sirenko
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia; Saint Petersburg State University, Universitetskaya nab., 7-9, Saint Petersburg 199034, Russia.
authors.forename: Armen O
authors.initials: AO
authors.lastname: Simonyan
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia; Saint Petersburg State University, Universitetskaya nab., 7-9, Saint Petersburg 199034, Russia.
authors.forename: Aleksey A
authors.initials: AA
authors.lastname: Chernev
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg 194064, Russia.
authors.forename: Olga E
authors.initials: OE
authors.lastname: Karpicheva
authors.affiliation: University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Piers
authors.affiliation: University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Redwood
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009218:Myosins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011817:Rabbits; D014335:Tropomyosin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D014335:Tropomyosin; D000251:Adenosine Triphosphatases; D009218:Myosins
keywords: Congenital myopathies; F-actin; Fluorescence polarization; Ghost muscle fibers; Myosin; Tropomyosin; Troponin