The human cardiac muscle ryanodine receptor-calcium release channel: Identification, primary structure and topological analysis

Richard E A Tunwell, Colin Wickenden, Bénédicte M A Bertrand, Valery I. Shevchenko, Martina B. Walsh, Paul D. Allen, F. Anthony Lai

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Rapid Ca2+ efflux from intracellular stores during cardiac muscle excitation-contraction coupling is mediated by the ryanodine-sensitive calcium-release channel, a large homotetrameric complex present in the sarcoplasmic reticulum. We report here the identification, primary structure and topological analysis of the ryanodine receptor-calcium release channel from human cardiac muscle (hRyR-2). Consistent with sedimentation and immunoblotting studies on the hRyR-2 protein, sequence analysis of ten overlapping cDNA clones reveals an open reading frame of 14901 nucleotides encoding a protein of 4967 amino acid residues with a predicted molecular mass of 564569 Da for hRyR-2. In-frame insertions corresponding to eight and ten amino acid residues were found in two of the ten cDNAs isolated, suggesting that novel, alternatively spliced transcripts of the hRyR-2 gene might exist. Six hydrophobic stretches, which are present within the hRyR-2 C-terminal 500 amino acids and are conserved in all RyR sequences, may be involved in forming the transmembrane domain that constitutes the Ca2+-conducting pathway, in agreement with competitive ELISA studies with a RyR-2-specific antibody. Sequence alignment of hRyR-2 with other RyR isoforms indicates a high level of overall identity within the RyR family, with the exception of two important regions that exhibit substantial variability. Phylogenetic analysis suggests that the RyR-2 isoform diverged from a single ancestral gene before the RyR-1 and RyR-3 isoforms to form a distinct branch of the RyR family tree.

Original languageEnglish (US)
Pages (from-to)477-487
Number of pages11
JournalBiochemical Journal
Volume318
Issue number2
StatePublished - Sep 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Tunwell, R. E. A., Wickenden, C., Bertrand, B. M. A., Shevchenko, V. I., Walsh, M. B., Allen, P. D., & Lai, F. A. (1996). The human cardiac muscle ryanodine receptor-calcium release channel: Identification, primary structure and topological analysis. Biochemical Journal, 318(2), 477-487.