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 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'A missense mutation in the seventh transmembrane domain constitutively activates the human Ca<sup>2+</sup> receptor'. Together they form a unique fingerprint.

  • Cite this