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A missense mutation in the seventh transmembrane domain constitutively activates the human Ca 2+ receptor
Author(s) -
Zhao Xin-mei,
Hauache Omar,
Goldsmith Paul K.,
Collins Regina,
Spiegel Allen M.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00368-3
Subject(s) - missense mutation , extracellular , transmembrane domain , receptor , mutant , alanine , mutation , enzyme linked receptor , point mutation , biology , transmembrane protein , microbiology and biotechnology , chemistry , biochemistry , amino acid , gene
A missense mutation, A843E, in the seventh transmembrane domain of the human Ca 2+ 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 Ca 2+ . A truncated human Ca 2+ receptor lacking the majority of the N‐terminal extracellular domain failed to respond to Ca 2+ 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 Ca 2+ receptor. Substitution of glutamate, but not lysine or valine, for alanine 843 leads to activation of the human Ca 2+ receptor in a manner that no longer depends upon Ca 2+ binding to the extracellular domain.