A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor

Xin Mei Zhao, Omar Hauache, Paul K. Goldsmith, Regina Collins, Allen M. Spiegel

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

A missense mutation, A843E, in the seventh transmembrane domain of the human Ca2+ receptor, identified in a subject with autosomal dominant hypocalcemia, was found to cause a constitutive activation while at the same time lowering the maximal response of the receptor to Ca2+. A truncated human Ca2+ receptor lacking the majority of the N-terminal extracellular domain failed to respond to Ca2+ despite an excellent cell surface expression. The A843E mutant version of this truncated receptor showed constitutive activation. These results identify A843 as a critical residue for maintaining the inactive conformation of the human Ca2+ receptor. Substitution of glutamate, but not lysine or valine, for alanine 843 leads to activation of the human Ca2+ receptor in a manner that no longer depends upon Ca2+ binding to the extracellular domain. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)180-184
Number of pages5
JournalFEBS Letters
Volume448
Issue number1
DOIs
StatePublished - Apr 2 1999
Externally publishedYes

Fingerprint

Missense Mutation
Chemical activation
Valine
Alanine
Lysine
Conformations
Glutamic Acid
Substitution reactions

Keywords

  • Calcium-sensing receptor
  • Constitutive activation
  • G protein-coupled receptor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor. / Zhao, Xin Mei; Hauache, Omar; Goldsmith, Paul K.; Collins, Regina; Spiegel, Allen M.

In: FEBS Letters, Vol. 448, No. 1, 02.04.1999, p. 180-184.

Research output: Contribution to journalArticle

Zhao, Xin Mei ; Hauache, Omar ; Goldsmith, Paul K. ; Collins, Regina ; Spiegel, Allen M. / A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor. In: FEBS Letters. 1999 ; Vol. 448, No. 1. pp. 180-184.
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