Evidence map›Paper›PMID 40749070›Full record

ArticleScience advances2025

Structural determinants of G protein subtype selectivity at the serotonin receptor 5-HT1A.

Audrey L Warren, Gregory Zilberg, Anwar Abbassi, Alejandro Abraham, Shifan Yang, Daniel Wacker

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Biased Signaling in Psychedelic Action.Annual review of pharmacology and toxicology · 2026
    Review
  3. 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

6 authors.

Audrey L WarrenDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-1538-8648
Gregory ZilbergDepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-6575-508X
Anwar AbbassiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alejandro AbrahamDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-5971-6834
Shifan YangDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-7616-1976
Daniel WackerDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-4951-7230

Funding

Structural Studies and Drug Discovery Illuminate Serotonin PharmacologyR35GM133504 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Daniel Wacker · 2019 to 2026
$3.4M
Training Program in Substance Use DisordersT32DA053558 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Paul J. Kenny · 2021 to 2026
$2.6M
Structural studies of psychedelic activity at the serotonin receptor 5-HT1AF31MH132317 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WARREN, AUDREY LOUISE · 2022 to 2023
$85k
NIDA NIH HHS T32 DA053558NIGMS NIH HHS R35 GM133504NIMH NIH HHS F31 MH132317
6 · The paper itself

Abstract

Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the receptor signals through inhibitory G proteins, more work is necessary to understand differences in transducer coupling and its relation to functional activity. To develop a molecular understanding of the differences underlying transducer coupling and activation, we performed structure-activity relationship studies of 5-HT1A with distinct G proteins. Through a combination of in vitro assays, we identified a potent partial agonist that selectively engages a G protein subtype. We further investigated the differences in G protein engagement at 5-HT1A with cryo-electron microscopy, determining structures of 5-HT1A bound to distinct ligands and G protein subtypes. Combined with subsequent structure-guided mutagenesis and signaling assays, our studies uncover both orthosteric and allosteric determinants of agonist-specific stimulation of distinct transducers.

Indexed as

GTP-Binding ProteinsReceptor, Serotonin, 5-HT1AAnimalsCryoelectron MicroscopyHEK293 CellsHumansLigandsModels, MolecularProtein BindingStructure-Activity RelationshipGTP-Binding ProteinsLigandsReceptor, Serotonin, 5-HT1A

Identifiers

PMID40749070
PMCPMC13155482

What OpenQuestion holds

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LicenceCC BY-NC
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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.