Molecular identification of the ryanodine receptor Ca super(2+) sensor

We have investigated the molecular basis for ryanodine receptor (RyR) activation by Ca super(2+) by using site-directed mutagenesis together with functional assays consisting of Ca super(2+) release measurements and single channel recordings in planar lipid bilayers. We report here that a single sub...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-06, Vol.273 (24), p.14675-14678
Main Authors: Chen, SRW, Ebisawa, K, Li, X, Zhang, L
Format: Article
Language:English
Online Access:Get full text
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Summary:We have investigated the molecular basis for ryanodine receptor (RyR) activation by Ca super(2+) by using site-directed mutagenesis together with functional assays consisting of Ca super(2+) release measurements and single channel recordings in planar lipid bilayers. We report here that a single substitution of alanine for glutamate at position 3885 (located in the putative transmembrane sequence M2 of the type 3 RyR) reduces the Ca super(2+) sensitivity, as measured by single channel activation, by more than 10,000-fold, without apparent changes in channel conductance and in modulation by other ligands (e.g. ATP and ryanodine). Co-expression of the wild type and mutant RyR proteins results in the synthesis of single channels that have intermediate Ca super(2+) sensitivities. These results suggest that the glutamates at position 3885 of each monomer may act in a coordinated way to form the Ca super(2+) sensor in the tetrameric structure corresponding to RyR.
ISSN:0021-9258