5XJM

Complex structure of angiotensin II type 2 receptor with Fab

Summary for 5XJM

• Entry DOI: 10.2210/pdb5xjm/pdb
• Related: 5XLI
• Descriptor: Type-2 angiotensin II receptor,Soluble cytochrome b562,Type-2 angiotensin II receptor, FabH, FabL, ... (4 entities in total)
• Functional Keywords: class a gpcr, regulate human blood pressure, angiotensin receptors, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 95665.45

Authors

Asada, H.,Horita, S.,Shimamura, T.,Iwata, S. (deposition date: 2017-05-02, release date: 2018-07-11, Last modification date: 2023-11-22)

Primary citation

Asada, H.,Horita, S.,Hirata, K.,Shiroishi, M.,Shiimura, Y.,Iwanari, H.,Hamakubo, T.,Shimamura, T.,Nomura, N.,Kusano-Arai, O.,Uemura, T.,Suno, C.,Kobayashi, T.,Iwata, S.
Crystal structure of the human angiotensin II type 2 receptor bound to an angiotensin II analog
Nat. Struct. Mol. Biol., 25:570-576, 2018

PubMed Abstract: Angiotensin II (AngII) plays a central role in regulating human blood pressure, which is mainly mediated by interactions between AngII and the G-protein-coupled receptors (GPCRs) AngII type 1 receptor (ATR) and AngII type 2 receptor (ATR). We have solved the crystal structure of human ATR binding the peptide ligand [Sar, Ile]AngII and its specific antibody at 3.2-Å resolution. [Sar, Ile]AngII interacts with both the 'core' binding domain, where the small-molecule ligands of ATR and ATR bind, and the 'extended' binding domain, which is equivalent to the allosteric modulator binding site of muscarinic acetylcholine receptor. We generated an antibody fragment to stabilize the extended binding domain that functions as a positive allosteric modulator. We also identified a signature positively charged cluster, which is conserved among peptide-binding receptors, to locate C termini at the bottom of the binding pocket. The reported results should help with designing ligands for angiotensin receptors and possibly to other peptide GPCRs.

PubMed: 29967536
DOI: 10.1038/s41594-018-0079-8

Experimental method

X-RAY DIFFRACTION (3.2 Å)