Evidence map›Paper›PMID 33296703›Full record

ArticleCell2020

How GPCR Phosphorylation Patterns Orchestrate Arrestin-Mediated Signaling.

Naomi R Latorraca, Matthieu Masureel, Scott A Hollingsworth, Franziska M Heydenreich, Carl-Mikael Suomivuori, Connor Brinton, Raphael J L Townshend, Michel Bouvier, Brian K Kobilka, Ron O Dror

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
8.9field-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

93 citing papers in PubMed, 169 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Factors modulating the assembly of human βNature structural & molecular biology · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Agonism and Biased Signaling.Handbook of experimental pharmacology · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

33 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 2 institutions in 2 countries.

Naomi R LatorracaDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA; Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Biophysics Program, Stanford University, Stanford, CA 94305, USA.
Matthieu MasureelDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: matthieu.masureel@gmail.com.
Scott A HollingsworthDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA; Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Franziska M HeydenreichDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Institute for Research in Immunology and Cancer, Université de Montreal, Montreal, QC, Canada.
Carl-Mikael SuomivuoriDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA; Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Connor BrintonDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA; Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Raphael J L TownshendDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA; Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michel BouvierDepartment of Biochemistry, Institute for Research in Immunology and Cancer, Université de Montreal, Montreal, QC, Canada.
Brian K KobilkaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ron O DrorDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA; Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Biophysics Program, Stanford University, Stanford, CA 94305, USA. Electronic address: ron.dror@stanford.edu.
Stanford University · USInstitute for Research in Immunology and Cancer · CA

Funding

THE MECHANISM OF BETA2 ADRENOCEPTOR ACTIVATIONR01NS028471 · NINDS · STANFORD UNIVERSITY · PI KOBILKA, BRIAN K · 1990 to 2021
$6.7M
Discovering the mechanism of GPCR-mediated arrestin stimulation to enable effective drug therapiesR01GM127359 · NIGMS · STANFORD UNIVERSITY · PI DROR, RON · 2018 to 2022
$1.5M
CIHR FDN148431NIGMS NIH HHS R01 GM127359NINDS NIH HHS R01 NS028471
6 · The paper itself

Abstract

Binding of arrestin to phosphorylated G-protein-coupled receptors (GPCRs) controls many aspects of cell signaling. The number and arrangement of phosphates may vary substantially for a given GPCR, and different phosphorylation patterns trigger different arrestin-mediated effects. Here, we determine how GPCR phosphorylation influences arrestin behavior by using atomic-level simulations and site-directed spectroscopy to reveal the effects of phosphorylation patterns on arrestin binding and conformation. We find that patterns favoring binding differ from those favoring activation-associated conformational change. Both binding and conformation depend more on arrangement of phosphates than on their total number, with phosphorylation at different positions sometimes exerting opposite effects. Phosphorylation patterns selectively favor a wide variety of arrestin conformations, differently affecting arrestin sites implicated in scaffolding distinct signaling proteins. We also reveal molecular mechanisms of these phenomena. Our work reveals the structural basis for the long-standing "barcode" hypothesis and has important implications for design of functionally selective GPCR-targeted drugs.

Indexed as

Signal TransductionArrestinComputer SimulationHEK293 CellsHumansPhosphatesPhosphopeptidesPhosphorylationProtein BindingProtein ConformationReceptors, G-Protein-CoupledSpectrum AnalysisArrestinPhosphatesPhosphopeptidesReceptors, G-Protein-Coupledall-atom molecular dynamics simulationbiased signalingfunctional selectivitypost-translational modificationprotein–protein interactionsseven-transmembrane receptor

Identifiers

PMID33296703
PMCPMC7901245
OpenAlexW3111854290

What OpenQuestion 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 OpenQuestion graph.