Evidence map›Paper›PMID 41264251›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Structural basis of modified ligand selectivity from N-terminal PAC1R alternative splicing.

Jessica J Lu, Giuseppe Deganutti, Miaomiao Li, Laura J Humphrys, Yandi Li, Theodore J Nettleton, Hariprasad Venugopal, Villy Julita, George Christopoulos, Christopher A Reynolds and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

14 authors.

Jessica J Lu *Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Giuseppe Deganutti *Centre for Health and Life Sciences, Coventry University, Coventry CV1 5FB, United Kingdom.ORCID 0000-0001-8780-2986
Miaomiao LiDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Laura J HumphrysDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Yandi LiDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Theodore J NettletonDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.ORCID 0009-0004-5843-2188
Hariprasad VenugopalRamaciotti Centre for Cryo Electron Microscopy, Monash University, Clayton, VIC 3800, Australia.
Villy JulitaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
George ChristopoulosDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Christopher A ReynoldsCentre for Health and Life Sciences, Coventry University, Coventry CV1 5FB, United Kingdom.ORCID 0000-0001-9267-5141
Patrick M SextonDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.ORCID 0000-0001-8902-2473
Denise WoottenDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Peishen ZhaoDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Sarah J PiperDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.ORCID 0000-0001-5337-5197

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The pituitary adenylate cyclase-activating polypeptide (PACAP) 1 receptor (PAC1R) is a class B1 G protein-coupled receptor activated by the endogenous peptide agonists PACAP and vasoactive intestinal peptide (VIP). Alternate splicing within the receptor extracellular domain (ECD) generates the PAC1R short variant (PAC1sR) that has selectively enhanced VIP function compared to the full-length, PAC1R null variant (PAC1nR). However, to date, a comprehensive pharmacological assessment of the downstream signaling outcomes of PAC1sR activation compared to PAC1nR has not been performed, and little information is available to mechanistically understand how ECD splicing may alter ligand engagement. Here, we demonstrated that VIP, but not PACAP, has globally enhanced activity across a broad range of functional endpoints at PAC1sR compared to PAC1nR. Cryo-EM structures of VIP-bound, stimulatory G protein (G

Indexed as

Alternative SplicingReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type IAnimalsCryoelectron MicroscopyHEK293 CellsHumansLigandsMolecular Dynamics SimulationPituitary Adenylate Cyclase-Activating PolypeptideProtein BindingSignal TransductionVasoactive Intestinal PeptideLigandsPituitary Adenylate Cyclase-Activating PolypeptideReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type IVasoactive Intestinal Peptidecryo-EMligand selectivitypituitary adenylate cyclase-activating polypeptide 1 receptorsplice variants

Identifiers

PMID41264251
PMCPMC12663942

What Socratic holds

Textmetadata
LicenceCC BY-NC-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 Socratic graph.