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Conversion of an inactive cardiac dihydropyridine receptor II-III loop segment into forms that activate skeletal ryanodine receptors

By Xinsheng Zhu, Georgina Gurrola, Ming Tao Jiang, Jeffery W. Walker and Hector H. Valdivia

Abstract

AbstractA 25 amino acid segment (Glu666–Pro691) of the II-III loop of the α1 subunit of the skeletal dihydropyridine receptor, but not the corresponding cardiac segment (Asp788–Pro814), activates skeletal ryanodine receptors. To identify the structural domains responsible for activation of skeletal ryanodine receptors, we systematically replaced amino acids of the cardiac II-III loop with their skeletal counterparts. A cluster of five basic residues of the skeletal II-III loop (681RKRRK685) was indispensable for activation of skeletal ryanodine receptors. In the cardiac segment, a negatively charged residue (Glu804) appears to diminish the electrostatic potential created by this basic cluster. In addition, Glu800 in the group of negatively charged residues 798EEEEE802 of the cardiac II-III loop may serve to prevent the binding of the activation domain

Publisher: Federation of European Biochemical Societies. Published by Elsevier B.V.
Year: 1999
DOI identifier: 10.1016/S0014-5793(99)00496-2
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