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

Structure. 2020 Apr 7;28(4):418-425.e4. doi: 10.1016/j.str.2019.12.003. Epub 2019 Dec 30.


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.

Keywords: G protein coupled receptor; X-ray crystal structure; angiotensin receptor; peptide hormon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / chemistry
  • Angiotensin II / metabolism
  • Animals
  • Binding Sites
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation*
  • Protein Binding
  • Receptor, Angiotensin, Type 2 / chemistry*
  • Receptor, Angiotensin, Type 2 / metabolism
  • Sf9 Cells
  • Spodoptera


  • Receptor, Angiotensin, Type 2
  • Angiotensin II