Evidence map›Paper›PMID 37163120›Full record

ArticlebioRxiv : the preprint server for biology2023

Conformational dynamics of the μ-opioid receptor determine ligand intrinsic efficacy.

Jiawei Zhao, Matthias Elgeti, Evan S O'Brien, Cecília P Sár, Amal Ei Daibani, Jie Heng, Xiaoou Sun, Tao Che, Wayne L Hubbell, Brian K Kobilka and 1 more

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

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 7 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 3 countries.

Jiawei ZhaoTsinghua-Peaking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University; Beijing, 100084, China.
Matthias ElgetiJules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California; Los Angeles, Los Angeles, CA 90095, USA.
Evan S O'BrienDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine; Stanford, CA 94305, USA.
Cecília P SárInstitute of Organic and Medicinal Chemistry, School of Pharmaceutical Sciences, University of Pécs; Szigeti st. 12, H-7624 Pécs, Hungary.
Amal Ei DaibaniDepartment of Anesthesiology, Washington University School of Medicine; Saint Louis, MO 63110, USA.
Jie HengTsinghua-Peaking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University; Beijing, 100084, China.
Xiaoou SunTsinghua-Peaking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University; Beijing, 100084, China.
Tao CheDepartment of Anesthesiology, Washington University School of Medicine; Saint Louis, MO 63110, USA.
Wayne L HubbellJules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California; Los Angeles, Los Angeles, CA 90095, USA.
Brian K KobilkaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine; Stanford, CA 94305, USA.
Chunlai ChenBeijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University; Beijing, 100084, China.
King Center · USDoheny Eye Institute · USStanford University · USWashington University in St. Louis · USCenter for Life Sciences · CNUniversity of Pecs · HU

Funding

Exploring the Conformational Landscape of G Protein Coupled ReceptorsR01GM137081 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ELGETI, AXEL PETER MATTHIAS · 2021 to 2022
$640k
NIGMS NIH HHS R01 GM137081
6 · The paper itself

Abstract

The μ-opioid receptor (μOR) is an important target for pain management and the molecular understanding of drug action will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance (DEER) and single-molecule fluorescence resonance energy transfer (smFRET), how ligand-specific conformational changes of the μOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several cytoplasmic receptor conformations interconverting on different timescales, including a pre-activated receptor conformation which is capable of G protein binding, and a fully activated conformation which dramatically lowers GDP affinity within the ternary complex. Interaction of β-arrestin-1 with the μOR core binding site appears less specific and occurs with much lower affinity than binding of G protein G

Identifiers

PMID37163120
PMCPMC10168371
OpenAlexW4367366180

What OpenQuestion holds

Textmetadata
LicenceCC BY-ND
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.