The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone.

Structure (London, England : 1993) 2020 Apr 07

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Angiotensin II (AngII) is a peptide hormone that plays a key role in regulating blood pressure, and its interactions with the G protein-coupled receptors, AngII type-1 receptor (AT1R) and AngII type-2 receptor (AT2R), are central to its mechanism of action. We solved the crystal structure of human AT2R bound to AngII and its specific antibody at 3.2-Å resolution. AngII (full agonist) and [Sar1, Ile8]-AngII (partial agonist) interact with AT2R in a similar fashion, except at the bottom of the AT2R ligand-binding pocket. In particular, the residues including Met1283.36, which constitute the deep end of the cavity, play important roles in angiotensin receptor (ATR) activation upon AngII binding. These differences that occur upon endogenous ligand binding may contribute to a structural change in AT2R, leading to normalization of the non-canonical coordination of helix 8. Our results will inform the design of more effective ligands for ATRs. Copyright © 2019 Elsevier Ltd. All rights reserved.

Citation

Hidetsugu Asada, Asuka Inoue, Francois Marie Ngako Kadji, Kunio Hirata, Yuki Shiimura, Dohyun Im, Tatsuro Shimamura, Norimichi Nomura, Hiroko Iwanari, Takao Hamakubo, Osamu Kusano-Arai, Hiromi Hisano, Tomoko Uemura, Chiyo Suno, Junken Aoki, So Iwata. The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone. Structure (London, England : 1993). 2020 Apr 07;28(4):418-425.e4