Evidence map›Paper›PMID 32079768›Full record

ArticleScience (New York, N.Y.)2020

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

Laura M Wingler, Meredith A Skiba, Conor McMahon, Dean P Staus, Alissa L W Kleinhenz, Carl-Mikael Suomivuori, Naomi R Latorraca, Ron O Dror, Robert J Lefkowitz, Andrew C Kruse

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed, 1 pooled it
13.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

140 citing papers in PubMed, 1 synthesis or guideline pooled it, 243 citations in OpenAlex.

  1. Direct Vascular Effects of Angiotensin II (A Systematic Short Review).International journal of molecular sciences · 2024
    Pooled it
  2. Article
  3. Activation of the angiotensin II type I receptor by a nonpeptide agonist.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Biased signalingActa pharmaceutica Sinica. B · 2025
    Review
  20. Article

80 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Laura M Wingler *Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.ORCID 0000-0002-3688-5088
Meredith A Skiba *Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-4615-6775
Conor McMahonDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9971-7869
Dean P StausHoward Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Alissa L W KleinhenzHoward Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.ORCID 0000-0001-5871-8216
Carl-Mikael SuomivuoriDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-2445-8791
Naomi R LatorracaDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-8310-8708
Ron O DrorDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-6418-2793
Robert J LefkowitzHoward Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. lefko001@receptor-biol.duke.edu andrew_kruse@hms.harvard.edu.ORCID 0000-0003-1472-7545
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. lefko001@receptor-biol.duke.edu andrew_kruse@hms.harvard.edu.ORCID 0000-0002-1467-1222
Howard Hughes Medical Institute · USHarvard University · USStanford University · US

Funding

Molecular Regulation of Cardiovascular 7 TM ReceptorsR01HL016037 · NHLBI · DUKE UNIVERSITY · PI ROBERT J LEFKOWITZ · 1985 to 2026
$14.5M
Molecular mechanisms of adiponectin signaling and PAQR functionDP5OD021345 · OD · HARVARD MEDICAL SCHOOL · PI KRUSE, ANDREW · 2015 to 2019
$2.1M
Discovering the mechanism of GPCR-mediated arrestin stimulation to enable effective drug therapiesR01GM127359 · NIGMS · STANFORD UNIVERSITY · PI DROR, RON · 2018 to 2022
$1.5M
Howard Hughes Medical InstituteNHLBI NIH HHS R01 HL016037NIGMS NIH HHS R01 GM127359NIH HHS DP5 OD021345
6 · The paper itself

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

Indexed as

Angiotensin IIbeta-ArrestinsHumansLigandsProtein ConformationReceptor, Angiotensin, Type 1Signal TransductionAngiotensin IIbeta-ArrestinsLigandsReceptor, Angiotensin, Type 1

Identifiers

PMID32079768
PMCPMC7171558
OpenAlexW3007079711

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.