Evidence map›Paper›PMID 21261298›Full record

ArticleBiochemistry2011

Making structural sense of dimerization interfaces of delta opioid receptor homodimers.

Jennifer M Johnston, Mahalaxmi Aburi, Davide Provasi, Andrea Bortolato, Eneko Urizar, Nevin A Lambert, Jonathan A Javitch, Marta Filizola

Open access · bronzeAbstract read
In one paragraph

Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Stabilized DNature communications · 2025
    Article
  4. Article
  5. Article
  6. The World of GPCR dimers - Mapping dopamine receptor DComputational and structural biotechnology journal · 2023
    Article
  7. Article
  8. Review
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  11. Article
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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

8 authors at 3 institutions in 1 country.

Jennifer M JohnstonDepartment of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, United States.
Mahalaxmi Aburi
Davide Provasi
Andrea Bortolato
Eneko Urizar
Nevin A Lambert
Jonathan A Javitch
Marta Filizola
Icahn School of Medicine at Mount Sinai · USColumbia University · USAugusta University · US

Funding

Structure of the Dopamine D2-Like Receptor Binding SitesR01MH054137 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI JAVITCH, JONATHAN A · 1995 to 2025
$12.0M
GPCR signaling complexes in living cellsR01GM078319 · NIGMS · AUGUSTA UNIVERSITY · PI LAMBERT, NEVIN ALAN · 2007 to 2017
$2.1M
OPIOID RECEPTOR OLIGOMERIZATION: PREDICTION & VALIDATIONR01DA020032 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI FILIZOLA, MARTA · 2006 to 2010
$1.5M
Molecular Determinants for the Action of PsychostimulantsK05DA022413 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI JAVITCH, JONATHAN A · 2007 to 2016
$1.3M
Structural Aspects of Oligomerization in the Function of GPCRsK02DA026434 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FILIZOLA, MARTA · 2009 to 2018
$1.2M
Hydrophobic mismatch and self-association of TM proteins and beta2 adrenoreceptorR01GM096762 · NIGMS · AUGUSTA UNIVERSITY · PI LAMBERT, NEVIN ALAN · 2011 to 2012
$373k
NIDA NIH HHS DA020032NIDA NIH HHS DA022413NIDA NIH HHS DA026434NIDA NIH HHS K05 DA022413NIDA NIH HHS R01 DA020032NIGMS NIH HHS GM078319NIGMS NIH HHS GM096762NIGMS NIH HHS R01 GM096762NIMH NIH HHS R01 MH054137
6 · The paper itself

Abstract

Opioid receptors, like other members of the G protein-coupled receptor (GPCR) family, have been shown to associate to form dimers and/or oligomers at the plasma membrane. Whether this association is stable or transient is not known. Recent compelling evidence suggests that at least some GPCRs rapidly associate and dissociate. We have recently calculated binding affinities from free energy estimates to predict transient association between mouse delta opioid receptor (DOR) protomers at a symmetric interface involving the fourth transmembrane (TM4) helix (herein termed "4" dimer). Here we present disulfide cross-linking experiments with DOR constructs with cysteines substituted at the extracellular ends of TM4 or TM5 that confirm the formation of DOR complexes involving these helices. Our results are consistent with the involvement of TM4 and/or TM5 at the DOR homodimer interface, but possibly with differing association propensities. Coarse-grained (CG) well-tempered metadynamics simulations of two different dimeric arrangements of DOR involving TM4 alone or with TM5 (herein termed "4/5" dimer) in an explicit lipid-water environment confirmed the presence of two structurally and energetically similar configurations of the 4 dimer, as previously assessed by umbrella sampling calculations, and revealed a single energetic minimum of the 4/5 dimer. Additional CG umbrella sampling simulations of the 4/5 dimer indicated that the strength of association between DOR protomers varies depending on the protein region at the interface, with the 4 dimer being more stable than the 4/5 dimer.

Indexed as

Protein MultimerizationAnimalsHEK293 CellsHumansMiceModels, MolecularProtein Structure, QuaternaryReceptors, Opioid, deltaDOR-1 protein, mouseReceptors, Opioid, delta

Identifiers

PMID21261298
PMCPMC3050604
OpenAlexW2003236921

What OpenQuestion holds

Textmetadata
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.