Evidence map›Paper›PMID 25445670›Full record

ArticleBiochimica et biophysica acta2015

Conserved disulfide bond is not essential for the adenosine A2A receptor: Extracellular cysteines influence receptor distribution within the cell and ligand-binding recognition.

Andrea N Naranjo, Amy Chevalier, Gregory D Cousins, Esther Ayettey, Emily C McCusker, Carola Wenk, Anne S Robinson

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

Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

6 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Functional Expression of Adenosine AInternational journal of molecular sciences · 2020
    Article
  4. Article
  5. Article
  6. Article
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

7 authors at 2 institutions in 1 country.

Andrea N NaranjoDepartment of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE 19716, USA. Electronic address: anaranjo@udel.edu.
Amy ChevalierDepartment of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE 19716, USA. Electronic address: amychev@seas.upenn.edu.
Gregory D CousinsDepartment of Computer Science, Tulane University, 6823 St. Charles Ave, New Orleans, LA 70118, USA.
Esther AyetteyDepartment of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE 19716, USA.
Emily C McCuskerDepartment of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE 19716, USA. Electronic address: emily.mccusker@tevapharm.com.
Carola WenkDepartment of Computer Science, Tulane University, 6823 St. Charles Ave, New Orleans, LA 70118, USA. Electronic address: cwenk@tulane.edu.
Anne S RobinsonDepartment of Chemical and Biomolecular Engineering, Tulane University, 300 Lindy Boggs Laboratory, 6823 St. Charles Ave, New Orleans, LA 70118, USA; Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE 19716, USA. Electronic address: asr@tulane.edu.
University of Delaware · USTulane University · US

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI MELINDA K DUNCAN · 2012 to 2026
$67.2M
COBRE on Membrane Protein Production and CharacterizationP30GM103519 · NIGMS · UNIVERSITY OF DELAWARE · PI LENHOFF, ABRAHAM M · 2012 to 2014
$3.3M
THE ROLE OF MITOCHONDRIAL TRANSPORT PROTEINS IN HEPATOCYTES AND ADIPOCYTESP30RR031160 · NCRR · UNIVERSITY OF DELAWARE · PI WOULFE, DONNA S · 2010 to 2011
$2.6M
NCRR NIH HHS P30 RR031160NIGMS NIH HHS P20 GM103446NIGMS NIH HHS P30 GM103519
6 · The paper itself

Abstract

G protein-coupled receptors (GPCRs) are integral membrane proteins involved in cellular signaling and constitute major drug targets. Despite their importance, the relationship between structure and function of these receptors is not well understood. In this study, the role of extracellular disulfide bonds on the trafficking and ligand-binding activity of the human A2A adenosine receptor was examined. To this end, cysteine-to-alanine mutations were conducted to replace individual and both cysteines in three disulfide bonds present in the first two extracellular loops. Although none of the disulfide bonds were essential for the formation of plasma membrane-localized active GPCR, loss of the disulfide bonds led to changes in the distribution of the receptor within the cell and changes in the ligand-binding affinity. These results indicate that in contrast to many class A GPCRs, the extracellular disulfide bonds of the A2A receptor are not essential, but can modulate the ligand-binding activity, by either changing the conformation of the extracellular loops or perturbing the interactions of the transmembrane domains.

Indexed as

AlanineAmino Acid SequenceAmino Acid SubstitutionCell MembraneCysteineDisulfidesGene ExpressionHEK293 CellsHumansKineticsLigandsModels, MolecularMolecular Sequence DataProtein BindingProtein Structure, SecondaryProtein TransportAlanineCysteineDisulfidesLigandsReceptor, Adenosine A2ARecombinant ProteinsAgonistConformational stabilityExtracellular loopG protein-coupled receptorHausdorff ratio

Identifiers

PMID25445670
PMCPMC4565196
OpenAlexW2072965094

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.