Evidence map›Paper›PMID 31141214›Full record

ArticleProteins2019

Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling.

Cheng Zhu, Qingjian Han, Alexander Samoshkin, Marino Convertino, Alexander Linton, Edgar M Faison, Ru-Rong Ji, Luda Diatchenko, Nikolay V Dokholyan

Open access · greenAbstract read
In one paragraph

Article in Proteins, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 37% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020
    Review
  4. Emerging Priorities for Microbiome Research.Frontiers in microbiology · 2020
    Review
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

9 authors at 4 institutions in 4 countries.

Cheng ZhuDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.ORCID 0000-0003-0260-6287
Qingjian HanDepartment of Anesthesiology, Duke University Medical Center, Durham, North Carolina.
Alexander SamoshkinAlan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
Marino ConvertinoDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Alexander LintonAlan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.ORCID 0000-0002-8939-7408
Edgar M FaisonDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Ru-Rong JiDepartment of Anesthesiology, Duke University Medical Center, Durham, North Carolina.
Luda DiatchenkoAlan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
Nikolay V DokholyanDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.ORCID 0000-0002-8225-4025
University of North Carolina at Chapel Hill · USDuke University · USMcGill University Health Centre · CAUniversity of Cambridge · GB

Funding

Engineering allostery for in vivo protein controlR01GM123247 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOKHOLYAN, NIKOLAY · 2017 to 2019
$1.5M
Integrating cheminformatics and molecular simulations for virtual drug screeningR01GM114015 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOKHOLYAN, NIKOLAY · 2016 to 2019
$1.1M
Development of a Novel Class for Opioid DrugsR41DA032293 · NIDA · ALGYNOMICS, INC. · PI DIATCHENKO, LUDA, DOKHOLYAN, NIKOLAY · 2012 to 2013
$657k
CIHR CERC09NIDA NIH HHS R41 DA032293NIGMS NIH HHS R01 GM114015NIGMS NIH HHS R01 GM123247NIH HHS GM123247NIH HHS R01GM114015NIH HHS STTR 1R41DA032293
6 · The paper itself

Abstract

The G protein-coupled μ-opioid receptor (μ-OR) mediates the majority of analgesia effects for morphine and other pain relievers. Despite extensive studies of its structure and activation mechanisms, the inherently low maturation efficiency of μ-OR represents a major hurdle to understanding its function. Here we computationally designed μ-OR mutants with altered stability to probe the relationship between cell-surface targeting, signal transduction, and agonist efficacy. The stabilizing mutation T315Y enhanced μ-OR trafficking to the plasma membrane and significantly promoted the morphine-mediated inhibition of downstream signaling. In contrast, the destabilizing mutation R165Y led to intracellular retention of μ-OR and reduced the response to morphine stimulation. These findings suggest that μ-OR stability is an important factor in regulating receptor signaling and provide a viable avenue to improve the efficacy of analgesics.

Indexed as

Protein ConformationHEK293 CellsHumansModels, MolecularProtein TransportReceptors, Opioid, muSignal TransductionReceptors, Opioid, muGPCRmaturationopioid receptorprotein engineeringsignal transduction

Identifiers

PMID31141214
PMCPMC6718349
OpenAlexW2947766366

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.