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 language | English (US) |
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Pages (from-to) | 180-184 |
Number of pages | 5 |
Journal | FEBS Letters |
Volume | 448 |
Issue number | 1 |
DOIs | |
State | Published - Apr 2 1999 |
Externally published | Yes |
Keywords
- Calcium-sensing receptor
- Constitutive activation
- G protein-coupled receptor
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology