Evidence map›Paper›PMID 36385145›Full record

ArticleNature communications2022

Understanding VPAC receptor family peptide binding and selectivity.

Sarah J Piper, Giuseppe Deganutti, Jessica Lu, Peishen Zhao, Yi-Lynn Liang, Yao Lu, Madeleine M Fletcher, Mohammed Akhter Hossain, Arthur Christopoulos, Christopher A Reynolds and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  3. Review
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  5. Article
  6. A chemogenetic approach for temporal and cell-specific activation of endogenous GPCRs in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Structural basis of modified ligand selectivity from N-terminal PAC1R alternative splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  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

13 authors at 8 institutions in 5 countries.

Sarah J PiperDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia.ORCID 0000-0001-5337-5197
Giuseppe DeganuttiCentre for Sport, Exercise and Life Sciences, Coventry University, CV1 5FB, Coventry, UK.ORCID 0000-0001-8780-2986
Jessica LuDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia.
Peishen ZhaoDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia.ORCID 0000-0003-0185-0595
Yi-Lynn LiangDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia.
Yao LuDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia.
Madeleine M FletcherDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia.ORCID 0000-0001-5519-4832
Mohammed Akhter HossainFlorey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia.ORCID 0000-0002-9961-0006
Arthur ChristopoulosDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia.ORCID 0000-0003-4442-3294
Christopher A ReynoldsCentre for Sport, Exercise and Life Sciences, Coventry University, CV1 5FB, Coventry, UK.ORCID 0000-0001-9267-5141
Radostin DanevGraduate School of Medicine, University of Tokyo, S402, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.ORCID 0000-0001-6406-8993
Patrick M SextonDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia. patrick.sexton@monash.edu.ORCID 0000-0001-8902-2473
Denise WoottenDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia. denise.wootten@monash.edu.ORCID 0000-0003-4563-1642
Monash University · AUDiscovery Institute · USAblynx (Belgium) · BECoventry University · GBGlaxoSmithKline (Australia) · AUThe University of Melbourne · AUThe University of Tokyo · JPUniversity of Essex · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite recent structural data, a comprehensive understanding of peptide binding and selectivity among different subfamily receptors is lacking. Here, we determine structures of active, Gs-coupled, VIP-VPAC1R, PACAP27-VPAC1R, and PACAP27-PAC1R complexes. Cryo-EM structural analyses and molecular dynamics simulations (MDSs) reveal fewer stable interactions between VPAC1R and VIP than for PACAP27, more extensive dynamics of VIP interaction with extracellular loop 3, and receptor-dependent differences in interactions of conserved N-terminal peptide residues with the receptor core. MD of VIP modelled into PAC1R predicts more transient VIP-PAC1R interactions in the receptor core, compared to VIP-VPAC1R, which may underlie the selectivity of VIP for VPAC1R over PAC1R. Collectively, our work improves molecular understanding of peptide engagement with the PAC1R and VPAC1R that may benefit the development of novel selective agonists.

Indexed as

Pituitary Adenylate Cyclase-Activating PolypeptideVasoactive Intestinal PeptideMolecular Dynamics SimulationProtein BindingPituitary Adenylate Cyclase-Activating PolypeptideVasoactive Intestinal Peptide

Identifiers

PMID36385145
PMCPMC9668914
OpenAlexW4309475330

What OpenQuestion 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 OpenQuestion graph.