Evidence map›Paper›PMID 41151574›Full record

ArticleStructure (London, England : 1993)2026

High throughput mutational characterization of the GPCR ligand C5a using yeast display and deep sequencing.

Yu Xu, Kaushik Thakkar, Li Guan, Yu Miao, Manal Mehibel, Robert B Lee, David Marciano, Vignesh Viswanathan, Ziwei Wang, Jinglong Wang and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2026. 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. Advances in Cyclic Peptides Targeting G Protein-Coupled Receptors.Chembiochem : a European journal of chemical biology · 2026
    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

28 authors.

Yu XuDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: yxu33@stanford.edu.
Kaushik ThakkarDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Li GuanDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Yu MiaoDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Manal MehibelDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Robert B LeeDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
David MarcianoDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Vignesh ViswanathanDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Ziwei WangDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Jinglong WangDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Lu JiDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Hongbin CaoDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Camille Fisher PetrakianDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Jocelyn ValenzuelaDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA.
Edward LaGoryDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Xianglian JiaDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Eui Jung MoonDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA; Department of Oncology, University of Oxford, Oxford, UK.
Rodolph MartinezDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Fang WuDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.
Richard L FrockDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Everett J ModingDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Quynh-Thu LeDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA; Department of Radiology, Stanford University, Stanford, CA, USA.
Erinn B RankinDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Cheng ZhangDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburg, PA, USA.
Possu HuangDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Monica M OlcinaDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA; Department of Oncology, University of Oxford, Oxford, UK.
Amato J GiacciaDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA; Department of Oncology, University of Oxford, Oxford, UK. Electronic address: giaccia@stanford.edu.
Edward E GravesDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA. Electronic address: egraves@stanford.edu.

Funding

Translational Biology CoreP01CA257907 · NCI · STANFORD UNIVERSITY · PI Quynh-Thu Xuan Le · 2022 to 2026
$12.0M
Structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) in inflammationR35GM128641 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHENG ZHANG · 2018 to 2026
$3.5M
NCI NIH HHS P01 CA257907NIGMS NIH HHS R35 GM128641
6 · The paper itself

Abstract

High-throughput mutagenesis approaches are widely employed to systematically characterize protein functions and play a critical role in therapeutic developments. As the largest class of membrane receptors, G protein-coupled receptors (GPCRs) are a primary focus of these studies. However, while significant progress has been made in understanding GPCRs themselves, mutagenesis studies on their ligands have lagged behind, because of the difficulties in solubilizing the target receptor. In this study, we present a novel approach that employs lipid vesicles to embed and stabilize target membrane receptors, allowing direct ligand screening. We applied this platform to investigate the anaphylatoxin complement 5a (C5a) and examined how mutations affect binding to its two native GPCRs: complement 5a receptor 1 (C5aR1) and complement 5a receptor 2 (C5aR2). The screening revealed new insights into the molecular basis of the interaction and led to the discovery of novel ligands that selectively activate C5aR2, but not C5aR1.

Indexed as

Complement C5aReceptor, Anaphylatoxin C5aBinding SitesHigh-Throughput Nucleotide SequencingHumansLigandsModels, MolecularMutationProtein BindingSaccharomyces cerevisiaeC5AR1 protein, humanC5aR2 protein, humanComplement C5aLigandsReceptor, Anaphylatoxin C5aG protein coupled receptorshigh throughput screeningsite saturation mutagenesisyeast surface display

Identifiers

PMID41151574
PMCPMC12671449

What OpenQuestion holds

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LicenceTDM
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.