| Structural highlights
Disease
AGTR2_HUMAN X-linked non-syndromic intellectual disability.
Function
AGTR2_HUMAN Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation.[1]
Publication Abstract from PubMed
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-A resolution. AngII (full agonist) and [Sar(1), Ile(8)]-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 Met128(3.36), 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.
The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone.,Asada H, Inoue A, Ngako Kadji FM, Hirata K, Shiimura Y, Im D, Shimamura T, Nomura N, Iwanari H, Hamakubo T, Kusano-Arai O, Hisano H, Uemura T, Suno C, Aoki J, Iwata S Structure. 2020 Apr 7;28(4):418-425.e4. doi: 10.1016/j.str.2019.12.003. Epub 2019, Dec 30. PMID:31899086[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nouet S, Amzallag N, Li JM, Louis S, Seitz I, Cui TX, Alleaume AM, Di Benedetto M, Boden C, Masson M, Strosberg AD, Horiuchi M, Couraud PO, Nahmias C. Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem. 2004 Jul 9;279(28):28989-97. Epub 2004 Apr 29. PMID:15123706 doi:http://dx.doi.org/10.1074/jbc.M403880200
- ↑ Asada H, Inoue A, Ngako Kadji FM, Hirata K, Shiimura Y, Im D, Shimamura T, Nomura N, Iwanari H, Hamakubo T, Kusano-Arai O, Hisano H, Uemura T, Suno C, Aoki J, Iwata S. The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone. Structure. 2020 Apr 7;28(4):418-425.e4. PMID:31899086 doi:10.1016/j.str.2019.12.003
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