PDBsum entry 6os0

Membrane protein

PDB id: 6os0

Contents

Protein chains

395 a.a.

126 a.a.

Ligands

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

NAG

Metals

_CL ×2

Waters ×18

PDB id:

6os0

Name:

Membrane protein

Title:

Structure of synthetic nanobody-stabilized angiotensin ii type 1 receptor bound to angiotensin ii

Structure:

Type-1 angiotensin ii receptor,soluble cytochrome b562 bril fusion protein. Chain: a. Synonym: at1ar,at1br,angiotensin ii type-1 receptor,at1,cytochrome b- 562. Engineered: yes. Nanobody nb.At110i1. Chain: d. Engineered: yes.

Source:

Homo sapiens, escherichia coli. Human. Organism_taxid: 9606, 562. Gene: agtr1, agtr1a, agtr1b, at2r1, at2r1b, cybc. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: expi293. Synthetic construct. Organism_taxid: 32630.

Resolution:

2.90Å R-factor: 0.265 R-free: 0.318

Authors:

L.M.Wingler,D.P.Staus,M.A.Skiba,C.Mcmahon,A.L.W.Kleinhenz, R.J.Lefkowitz,A.C.Kruse

Key ref:

L.M.Wingler et al. (2020). Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR. Science, 367, 888-892. PubMed id: 32079768 DOI: 10.1126/science.aay9813

Date:

01-May-19 Release date: 19-Feb-20

Protein chain

P0ABE7  (C562_ECOLX) -  Soluble cytochrome b562 from Escherichia coli

Seq: 128 a.a.

Struc: 395 a.a.*

Protein chain

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

Seq: 359 a.a.

Struc: 395 a.a.*

Protein chain

No UniProt id for this chain

Struc: 126 a.a.

* PDB and UniProt seqs differ at 112 residue positions (black crosses)

DOI no: 10.1126/science.aay9813

Science 367:888-892 (2020)

PubMed id: 32079768

Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR.

L.M.Wingler, M.A.Skiba, C.McMahon, D.P.Staus, A.L.W.Kleinhenz, C.M.Suomivuori, N.R.Latorraca, R.O.Dror, R.J.Lefkowitz, A.C.Kruse.

ABSTRACT

Biased agonists of G protein-coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly β-arrestin-biased analogs. Compared with other ligands, AngII promotes more-substantial rearrangements not only at the bottom of the ligand-binding pocket but also in a key polar network in the receptor core, which forms a sodium-binding site in most GPCRs. Divergences from the family consensus in this region, which appears to act as a biased signaling switch, may predispose the AT1R and certain other GPCRs (such as chemokine receptors) to adopt conformations that are capable of activating β-arrestin but not heterotrimeric G_q protein signaling.