Evidence map›Paper›PMID 40930102›Full record

ArticleCell genomics2025

A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor.

Ann Lin, Kaitlyn Spees, Raeline Valbuena, Jakob Wirbel, Aravind Natarajan, Nora Enright, Ami S Bhatt, Michael C Bassik

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 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. Review
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

8 authors.

Ann LinDepartment of Genetics, Stanford University, Stanford, CA, USA.
Kaitlyn SpeesDepartment of Genetics, Stanford University, Stanford, CA, USA.
Raeline ValbuenaDepartment of Genetics, Stanford University, Stanford, CA, USA.
Jakob WirbelDepartment of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.
Aravind NatarajanDepartment of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.
Nora EnrightDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Ami S BhattDepartment of Genetics, Stanford University, Stanford, CA, USA; Department of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA. Electronic address: asbhatt@stanford.edu.
Michael C BassikDepartment of Genetics, Stanford University, Stanford, CA, USA. Electronic address: bassik@stanford.edu.

Funding

INSTITUTIONAL TRAINING GRANT IN GENOME SCIENCET32HG000044 · NHGRI · STANFORD UNIVERSITY · PI MICHAEL P. SNYDER · 1995 to 2026
$32.2M
High-throughput development and characterization of compact tools for transcriptional and chromatin perturbationsR01HG011866 · NHGRI · STANFORD UNIVERSITY · PI MICHAEL C BASSIK, Lacramioara Bintu · 2021 to 2026
$6.9M
Culture-free pathogen tracking in hospitalized patientsR01AI143757 · NIAID · STANFORD UNIVERSITY · PI BHATT, AMI SIDDHARTH · 2020 to 2023
$3.0M
Emerging novel mechanisms of antibiotic resistance in the prevalent foodborne pathogen, SalmonellaR01AI148623 · NIAID · STANFORD UNIVERSITY · PI BHATT, AMI SIDDHARTH · 2019 to 2023
$2.0M
NHGRI NIH HHS R01 HG011866NHGRI NIH HHS T32 HG000044NIAID NIH HHS R01 AI143757NIAID NIH HHS R01 AI148623
6 · The paper itself

Abstract

Non-olfactory G-protein-coupled receptors (GPCRs) regulate vital physiological functions and are targets for ∼34% of US Food and Drug Administration (FDA)-approved drugs. While small-molecule-activated GPCRs are well studied, there is growing interest in peptide GPCRs, particularly the melanocortin-4 receptor (MC4R), a key regulator of energy balance and appetite. Activation of MC4R by β-melanocyte-stimulating hormone (β-MSH) reduces food intake, and pathway dysfunction leads to obesity. However, current methods to study GPCR-peptide interactions are resource intensive and low throughput. To address this, we developed a high-throughput cell surface peptide display platform with a β-arrestin-based MC4R reporter to screen over 2,000 β-MSH point mutants. This approach identified peptide variants that significantly impact MC4R activation, including a novel D5H mutant with enhanced receptor activation. Our results demonstrate a scalable method to directly link GPCR activation to peptide variants, offering insights for therapeutic peptide design.

Indexed as

beta-MSHPeptidesReceptor, Melanocortin, Type 4beta-ArrestinsHEK293 CellsHumansMutationbeta-Arrestinsbeta-MSHMC4R protein, humanPeptidesReceptor, Melanocortin, Type 4MC4Rpeptide displayscanning mutagenesis

Identifiers

PMID40930102
PMCPMC12648107

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.