Angiotensin II type 1 receptor‐function affected by mutations in cytoplasmic loop CD

FEBS Letters

Zhang, Jingli¹  Karnik, Sadashiva S¹  Miura, Shin-ichiro¹ 

[1] Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, NB50, Cleveland, OH 44195, USA

关键词: Angiotensin II;    G protein coupling;    metal–ion binding site;    Peptide hormone receptor activation;    CD-loop;    EF-loop;    Ang II;    angiotensin II;    GPCR;    G protein coupled receptor;    AT1;    Ang II type 1 receptor;    IP;    inositol phosphate;    DMEM;    Dulbecco's modified minimal essential medium;    CPM;    counts per minute;   

DOI  :  10.1016/S0014-5793(00)01346-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (AT₁) 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 ZnCl₂. Inhibition by ZnCl₂ 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 Tyr¹²⁷ to Ile¹³⁰ is important for G_q/11 activation by the AT₁ receptor.

【 授权许可】

Unknown