FEBS Letters | |
A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor | |
Spiegel, Allen M.1  Zhao, Xin-mei1  Hauache, Omar1  Goldsmith, Paul K.1  Collins, Regina1  | |
[1] Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9N-222, Bethesda, MD 20892, USA | |
关键词: G protein-coupled receptor; Constitutive activation; Calcium-sensing receptor; CaR; Ca2+ receptor; hCaR; human Ca2+ receptor; DMEM; Dulbecco's modified Eagle's medium; FBS; fetal bovine serum; ADH; autosomal dominant hypocalcemia; PI; phosphoinositide; GPCR; G protein-coupled receptor; ECD; extracellular domain; PCR; polymerase chain reaction; TM; transmembrane domain; mGluR; metabotropic glutamate receptor; | |
DOI : 10.1016/S0014-5793(99)00368-3 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
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.
【 授权许可】
Unknown
【 预 览 】
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RO201912020307534ZK.pdf | 133KB | download |