Evidence map›Paper›PMID 34531301›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

A membrane protein display platform for receptor interactome discovery.

Shengya Cao, Sean M Peterson, Sören Müller, Mike Reichelt, Christian McRoberts Amador, Nadia Martinez-Martin

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 49 citations in OpenAlex.

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  10. Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025
    Review
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  14. B7 homolog 3 in pancreatic cancer.World journal of gastroenterology · 2024
    Review
  15. Journal of proteome research · 2024
    Review
  16. 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

6 authors at 2 institutions in 2 countries.

Shengya CaoMicrochemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA 94080; mrtn.nm32@gmail.com cao.shengya@gene.com.ORCID 0000-0002-4717-4927
Sean M PetersonMicrochemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA 94080.
Sören MüllerOncology Bioinformatics, Genentech, South San Francisco, CA 94080.
Mike ReicheltPathology Labs, Genentech, South San Francisco, CA 94080.
Christian McRoberts AmadorBiomedical Engineering, Duke University, Durham, NC 27708.
Nadia Martinez-MartinMicrochemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA 94080; mrtn.nm32@gmail.com cao.shengya@gene.com.
Almirall (Spain) · ESDuke University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cell surface receptors are critical for cell signaling and constitute a quarter of all human genes. Despite their importance and abundance, receptor interaction networks remain understudied because of difficulties associated with maintaining membrane proteins in their native conformation and their typically weak interactions. To overcome these challenges, we developed an extracellular vesicle-based method for membrane protein display that enables purification-free and high-throughput detection of receptor-ligand interactions in membranes. We demonstrate that this platform is broadly applicable to a variety of membrane proteins, enabling enhanced detection of extracellular interactions over a wide range of binding affinities. We were able to recapitulate and expand the interactome for prominent members of the B7 family of immunoregulatory proteins such as PD-L1/CD274 and B7-H3/CD276. Moreover, when applied to the orphan cancer-associated fibroblast protein, LRRC15, we identified a membrane-dependent interaction with the tumor stroma marker TEM1/CD248. Furthermore, this platform enabled profiling of cellular receptors for target-expressing as well as endogenous extracellular vesicles. Overall, this study presents a sensitive and easy to use screening platform that bypasses membrane protein purification and enables characterization of interactomes for any cell surface-expressed target of interest in its native state.

Indexed as

Protein Interaction Domains and MotifsAntigens, CDAntigens, NeoplasmB7 AntigensB7-H1 AntigenHEK293 CellsHumansMembrane ProteinsAntigens, CDAntigens, NeoplasmB7 AntigensB7-H1 AntigenCD248 protein, humanCD274 protein, humanCD276 protein, humanLRRC15 protein, humanMembrane Proteinsextracellular vesiclehigh-throughput screeningmembrane proteinreceptor–ligand interaction

Identifiers

PMID34531301
PMCPMC8488672
OpenAlexW3199513060

What OpenQuestion 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 OpenQuestion graph.