Identification of the cysteine residues in the amino-terminal extracellular domain of the human Ca2+ receptor critical for dimerization. Implications for function of monomeric Ca2+ receptor

Kausik Ray, Benjamin C. Hauschild, Peter J. Steinbach, Paul K. Goldsmith, Omar Hauache, Allen M. Spiegel

Research output: Contribution to journalArticle

160 Scopus citations


We analyzed the effect of substituting serine for each of the 19 cysteine residues within the amino-terminal extracellular domain of the human Ca2+ receptor on cell surface expression and receptor dimerization. C129S, C131S, C437S, C449S, and C482S were similar to wild type receptor; the other 14 cysteine to serine mutants were retained intracellularly. Four of these, C60S, C101S, C358S and C395S, were unable to dimerize. A C129S/C131S double mutant failed to dimerize but was unique in that the monomeric form expressed at the cell surface. Substitution of a cysteine for serine 132 within the C129S/C131S mutant restored receptor dimerization. Mutation of residues Cys- 129, Cys-131, and Set-132, singly and in various combinations caused a left shift in Ca2+ response compared with wild type receptor. These results identify cysteines 129 and 131 as critical in formation of intermolecular disulfide bond(s) responsible for receptor dimerization. In a 'venus flytrap' model of the receptor extracellular domain, Cys-129 and Cys-131 are located within a region protruding from one lobe of the flytrap. We suggest that this region represents a dimer interface for the receptor and that mutation of residues within the interface causes important changes in Ca2+ response of the receptor.

Original languageEnglish (US)
Pages (from-to)27642-27650
Number of pages9
JournalJournal of Biological Chemistry
Issue number39
StatePublished - Sep 24 1999


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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