Evidence map›Paper›PMID 37736747›Full record

ArticleNature communications2023

Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding.

Shota Suzuki, Kotaro Tanaka, Kouki Nishikawa, Hiroshi Suzuki, Atsunori Oshima, Yoshinori Fujiyoshi

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

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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

6 authors at 4 institutions in 1 country.

Shota SuzukiTMDU Advanced Research Institute, Tokyo Medical and Dental University Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-6516-8424
Kotaro TanakaCellular and Structural Physiology Institute (CeSPI), Nagoya University, Nagoya, Japan.
Kouki NishikawaJoint Research Course for Advanced Biomolecular Characterization, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Hiroshi SuzukiTMDU Advanced Research Institute, Tokyo Medical and Dental University Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0001-5371-6385
Atsunori OshimaCellular and Structural Physiology Institute (CeSPI), Nagoya University, Nagoya, Japan.ORCID http://orcid.org/0000-0003-1174-1368
Yoshinori FujiyoshiTMDU Advanced Research Institute, Tokyo Medical and Dental University Bunkyo-ku, Tokyo, Japan. yoshi.cesp@tmd.ac.jp.ORCID http://orcid.org/0000-0002-8070-1493
Tokyo Medical and Dental University · JPGifu University · JPNagoya University · JPTokyo University of Agriculture and Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms.

Indexed as

Amino AcidsSignal TransductionAminesArginineHumansLigandsAminesAmino AcidsArginineLigands

Identifiers

PMID37736747
PMCPMC10516952
OpenAlexW4386944943

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.