A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor
| Autor: | Xin Mei Zhao, Regina M. Collins, Paul K. Goldsmith, Omar Hauache, Allen M. Spiegel |
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| Rok vydání: | 1999 |
| Předmět: |
Mutant
Biophysics Mutation Missense Enzyme-Linked Immunosorbent Assay Biology Phosphatidylinositols Biochemistry Constitutive activation Structural Biology Calcium-sensing receptor Genetics Missense mutation Humans 5-HT5A receptor G protein-coupled receptor Receptor Molecular Biology Cell Line Transformed Binding Sites Hydrolysis Calcium-Binding Proteins Cell Membrane Cell Biology Cell biology Transmembrane domain Signal transduction Signal Transduction |
| Zdroj: | FEBS letters. 448(1) |
| ISSN: | 0014-5793 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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