PDBsum entry 1zv0

Signaling protein

PDB id: 1zv0

Contents

Protein chain

359 a.a.

Ligands

ASP-ARG-VAL-TYR-ILE-HIS-PRO-PBF

Theoretical model

PDB id:

1zv0

Name:

Signaling protein

Title:

Molecular model of a complex between [sar1, bpa8]angii and hat1 receptor

Structure:

[Sar1, bpa8] angiotensin ii. Chain: a. Engineered: yes. Type-1 angiotensin ii receptor. Chain: b. Synonym: at1. At1ar

Source:

Synthetic: yes. Other_details: modified residues : sarcosine 1, p- benzoylphenylalanine (bpa) 8. Homo sapiens. Human

Authors:

M.Clement,S.S.Martin,M.E.Beaulieu,C.Chamberland,P.Lavigne, R.Leduc,G.Guillemette,E.Escher

Key ref:

M.Clément et al. (2005). Determining the environment of the ligand binding pocket of the human angiotensin II type I (hAT1) receptor using the methionine proximity assay. J Biol Chem, 280, 27121-27129. PubMed id: 15890659 DOI: 10.1074/jbc.M413653200

Date:

01-Jun-05 Release date: 21-Jun-05

Protein chain

P30556  (AGTR1_HUMAN) -  Type-1 angiotensin II receptor from Homo sapiens

Seq: 359 a.a.

Struc: 359 a.a.

DOI no: 10.1074/jbc.M413653200

J Biol Chem 280:27121-27129 (2005)

PubMed id: 15890659

Determining the environment of the ligand binding pocket of the human angiotensin II type I (hAT1) receptor using the methionine proximity assay.

M.Clément, S.S.Martin, M.E.Beaulieu, C.Chamberland, P.Lavigne, R.Leduc, G.Guillemette, E.Escher.

ABSTRACT

The peptide hormone angiotensin II (AngII) binds to the AT0 (angiotensin type 1) receptor within the transmembrane domains in an extended conformation, and its C-terminal residue interacts with transmembrane domain VII at Phe-293/Asn-294. The molecular environment of this binding pocket remains to be elucidated. The preferential binding of benzophenone photolabels to methionine residues in the target structure has enabled us to design an experimental approach called the methionine proximity assay, which is based on systematic mutagenesis and photolabeling to determine the molecular environment of this binding pocket. A series of 44 transmembrane domain III, VI, and VII X --> Met mutants photolabeled either with 125I-[Sar1,p'-benzoyl-L-Phe8]AngII or with 125I-[Sar1,p''-methoxy-p'-benzoyl-L-Phe8]AngII were purified and digested with cyanogen bromide. Several mutants produced digestion patterns different from that observed with wild type human AT1, indicating that they had a new receptor contact with position 8 of AngII. The following residues form this binding pocket: L112M and Y113M in transmembrane domain (TMD) III; F249M, W253M, H256M, and T260M in TMD VI; and F293M, N294M, N295M, C296M, and L297M in TMD VII. Homology modeling and incorporation of these contacts allowed us to develop an evidence-based molecular model of interactions with human AT1 that is very similar to the rhodopsin-retinal interaction.

Selected figure(s)

Figure 6.
FIG. 6. Reaction scheme of photoactivated Bpa with a Met residue and the ensuring CNBr cleavage products. The asterisk (*) indicates a radioactive label for autoradiographic detection. The -pathway produces labeled protein fragments only, and the pathway produces ligand release.

Figure 7.
FIG. 7. Molecular model of the [Sar1,Bpa^8]AngII-liganded hAT[1] receptor. A, side view. The receptor backbone is shown in gray, Met-mutated residues are either blue (MPA-negative) or green (MPA-positive). The ligand is shown in yellow with a mesh surface of the benzophenone residue. For clarity, the ligand side chains are omitted except for the Bpa residue in position 8. B, top view of the transmembrane section; color identification is the same as described for panel A. Only the position of the Bpa residue is shown.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 27121-27129) copyright 2005.

Figures were selected by an automated process.