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Angiotensin II type 1 receptor‐function affected by mutations in cytoplasmic loop CD
Author(s) -
Miura Shin-ichiro,
Zhang Jingli,
Karnik Sadashiva S
Publication year - 2000
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(00)01346-6
Subject(s) - mutant , receptor , angiotensin ii , chemistry , wild type , cytoplasm , inositol phosphate , microbiology and biotechnology , biology , inositol , biochemistry , gene
To explore peptide hormone‐induced conformational changes, we attempted to engineer a metal–ion binding site between the cytoplasmic loops CD and EF in the angiotensin II type 1 (AT 1 ) receptor. We constructed 12 double and six triple histidine mutant receptors, and tested the ability of each mutant and the wild‐type to activate inositol phosphate (IP) production with and without ZnCl 2 . Inhibition by ZnCl 2 in the double and triple His mutant receptors was not significant, but these mutations directly decreased the IP production. Systematic analysis of single His mutants demonstrated that the loop CD‐mutants displayed 52–74% inhibition of IP production, whereas the loop EF‐mutants did not affect IP production. These results indicate that the cytoplasmic loop CD‐segment from Tyr 127 to Ile 130 is important for G q/11 activation by the AT 1 receptor.