Charged surface area of maurocalcine determines its interaction with the skeletal ryanodine receptor |
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Authors: | Lukács Balázs Sztretye Mónika Almássy János Sárközi Sándor Dienes Beatrix Mabrouk Kamel Simut Cecilia Szabó László Szentesi Péter De Waard Michel Ronjat Michel Jóna István Csernoch László |
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Institution: | * Department of Physiology, Research Centre for Molecular Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary † Institut National de la Santé et de la Recherche Médicale, U836, Grenoble, France ‡ Institut des Neurosciences, Université Joseph Fourier, Grenoble, France § Universités D’Aix-Marseille 1, 2 et 3 Centre National de la Recherche Scientifique-Unite Mixte de Recherche 6517 “Chimie, Biologie et Radicaux Libres,” Marseille, France ¶ Department of Electrical Engineering, Sapientia Hungarian University of Transylvania, Targu Mures, Romania |
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Abstract: | The 33 amino acid scorpion toxin maurocalcine (MCa) has been shown to modify the gating of the skeletal-type ryanodine receptor (RyR1). Here we explored the effects of MCa and its mutants (Ala8]MCa, Ala19]MCa, Ala20]MCa, Ala22]MCa, Ala23]MCa, and Ala24]MCa) on RyR1 incorporated into artificial lipid bilayers and on elementary calcium release events (ECRE) in rat and frog skeletal muscle fibers. The peptides induced long-lasting subconductance states (LLSS) on RyR1 that lasted for several seconds. However, their average length and frequency were decreased if the mutation was placed farther away in the 3D structure from the critical 24Arg residue. The effect was strongly dependent on the direction of the current through the channel. If the direction was similar to that followed by calcium during release, the peptides were 8- to 10-fold less effective. In fibers long-lasting calcium release events were observed after the addition of the peptides. The average length of these events correlated well with the duration of LLSS. These data suggest that the effect of the peptide is governed by the large charged surface formed by residues Lys20, Lys22, Arg23, Arg24, and Lys8. Our observations also indicate that the results from bilayer experiments mimic the in situ effects of MCa on RyR1. |
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