Evidence map›Paper›PMID 21956331›Full record

ArticleNature2011

Conformational changes in the G protein Gs induced by the β2 adrenergic receptor.

Ka Young Chung, Søren G F Rasmussen, Tong Liu, Sheng Li, Brian T DeVree, Pil Seok Chae, Diane Calinski, Brian K Kobilka, Virgil L Woods, Roger K Sunahara

Abstract read
In one paragraph

Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
215citing papers in PubMed, 1 pooled it
16.1field-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

215 citing papers in PubMed, 1 synthesis or guideline pooled it, 375 citations in OpenAlex.

  1. Pooled it
  2. Ligand-dependent G protein dynamics underlying opioid efficacy.Nature structural & molecular biology · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Ligand-dependent G protein dynamics underlying opioid signaling efficacy.bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. A molten globule ensemble primes Arf1-GDP for the nucleotide switch.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Stabilization of interdomain closure by a G protein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

Ka Young ChungDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Søren G F Rasmussen
Tong Liu
Sheng Li
Brian T DeVree
Pil Seok Chae
Diane Calinski
Brian K Kobilka
Virgil L Woods
Roger K Sunahara
University of California, San Diego · USUniversity of Michigan–Ann Arbor · USStanford University · USHanyang University · KRUniversity of Copenhagen · DK

Funding

PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Role of complement in kidney disorders: from hemodialysis to transportationP01AI068730 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2007 to 2018
$16.0M
Structure and dynamics of G protein coupled receptor-G protein complexesR01GM083118 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOBILKA, BRIAN K, SKINIOTIS, GEORGIOS · 2008 to 2023
$8.3M
ACTION OF LIPOLYTIC ENZYMESR01GM020501 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 1985 to 2020
$7.3M
THE MECHANISM OF BETA2 ADRENOCEPTOR ACTIVATIONR01NS028471 · NINDS · STANFORD UNIVERSITY · PI KOBILKA, BRIAN K · 1990 to 2021
$6.7M
Epac/cAMP-GEF, A Novel Intracellular cAMP ReceptorR01GM066170 · NIGMS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI CHENG, XIAODONG · 2003 to 2017
$4.6M
MICHIGAN MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008270 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BROOKS, CHARLES L · 1988 to 2012
$4.5M
Beta2 Adrenoceptor Structure and Mechanism of ActivationR37NS028471 · NINDS · STANFORD UNIVERSITY · PI KOBILKA, BRIAN K · 2005 to 2011
$3.9M
Regulation, Signaling, and Dynamics of Glucan PhosphatasesR01NS070899 · NINDS · UNIVERSITY OF KENTUCKY · PI GENTRY, MATTHEW S. · 2010 to 2019
$3.6M
Beta Adrenoceptor Signaling Complexes in Innervated Cardiac MyocytesR01HL071078 · NHLBI · STANFORD UNIVERSITY · PI KOBILKA, BRIAN K · 2002 to 2012
$3.5M
STRUCTURE DRIVEN ANALYSIS OF EBOLA VIRUS RECEPTOR BINDING SITER01AI081982 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI SAPHIRE, ERICA OLLMANN · 2010 to 2014
$2.8M
Thermodynamic and structural studies on the formation of the C3 convertaseR01AI072106 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2007 to 2011
$2.0M
NCI NIH HHS CA118595NCRR NIH HHS RR029388NCRR NIH HHS S10 RR029388NHLBI NIH HHS HL071078NIAID NIH HHS AI076961NIAID NIH HHS AI081982NIAID NIH HHS AI2008031NIAID NIH HHS P01 AI068730NIAID NIH HHS R01 AI072106NIAID NIH HHS R01 AI081982NIDDK NIH HHS P60 DK020572NIDDK NIH HHS P60DK-20572NIGMS NIH HHS F32 GM020501NIGMS NIH HHS GM008270NIGMS NIH HHS GM066170NIGMS NIH HHS GM068603NIGMS NIH HHS GM083118NIGMS NIH HHS GM093325NIGMS NIH HHS GM20501NIGMS NIH HHS R01 GM020501NIGMS NIH HHS R01 GM066170NIGMS NIH HHS R01 GM068603NIGMS NIH HHS R01 GM083118NIGMS NIH HHS R01 GM093325NIGMS NIH HHS T32 GM008270NINDS NIH HHS NS28471NINDS NIH HHS R01 NS028471NINDS NIH HHS R01 NS070899NINDS NIH HHS R37 NS028471
6 · The paper itself

Abstract

G protein-coupled receptors represent the largest family of membrane receptors that instigate signalling through nucleotide exchange on heterotrimeric G proteins. Nucleotide exchange, or more precisely, GDP dissociation from the G protein α-subunit, is the key step towards G protein activation and initiation of downstream signalling cascades. Despite a wealth of biochemical and biophysical studies on inactive and active conformations of several heterotrimeric G proteins, the molecular underpinnings of G protein activation remain elusive. To characterize this mechanism, we applied peptide amide hydrogen-deuterium exchange mass spectrometry to probe changes in the structure of the heterotrimeric bovine G protein, Gs (the stimulatory G protein for adenylyl cyclase) on formation of a complex with agonist-bound human β(2) adrenergic receptor (β(2)AR). Here we report structural links between the receptor-binding surface and the nucleotide-binding pocket of Gs that undergo higher levels of hydrogen-deuterium exchange than would be predicted from the crystal structure of the β(2)AR-Gs complex. Together with X-ray crystallographic and electron microscopic data of the β(2)AR-Gs complex (from refs 2, 3), we provide a rationale for a mechanism of nucleotide exchange, whereby the receptor perturbs the structure of the amino-terminal region of the α-subunit of Gs and consequently alters the 'P-loop' that binds the β-phosphate in GDP. As with the Ras family of small-molecular-weight G proteins, P-loop stabilization and β-phosphate coordination are key determinants of GDP (and GTP) binding affinity.

Indexed as

Adrenergic beta-2 Receptor AgonistsAnimalsBiocatalysisCatalytic DomainCattleCrystallography, X-RayDeuterium Exchange MeasurementGTP-Binding Protein alpha Subunits, GsGuanosine DiphosphateGuanosine TriphosphateHumansModels, MolecularProtein BindingProtein ConformationReceptors, Adrenergic, beta-2Adrenergic beta-2 Receptor AgonistsGTP-Binding Protein alpha Subunits, GsGuanosine DiphosphateGuanosine TriphosphateReceptors, Adrenergic, beta-2

Identifiers

PMID21956331
PMCPMC3448949
OpenAlexW2064664612

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.