Evidence map›Paper›PMID 38480980›Full record

ArticleNature chemical biology2024

De novo-designed transmembrane proteins bind and regulate a cytokine receptor.

Marco Mravic, Li He, Huong T Kratochvil, Hailin Hu, Sarah E Nick, Weiya Bai, Anne Edwards, Hyunil Jo, Yibing Wu, Daniel DiMaio and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

17 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
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  3. Article
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  5. Review
  6. Review
  7. bioRxiv : the preprint server for biology · 2026
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Design principles of the common Gly-X6-Gly membrane protein building block.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. TheViruses · 2024
    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

11 authors at 5 institutions in 2 countries.

Marco Mravic *Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA. mmravic@scripps.edu.ORCID 0000-0001-6294-1824
Li He *Department of Genetics, Yale School of Medicine, New Haven, CT, USA.ORCID 0009-0009-3501-5281
Huong T KratochvilDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA.
Hailin HuDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA.ORCID 0000-0002-5768-4437
Sarah E NickDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA.ORCID 0000-0001-9683-7195
Weiya BaiDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Anne EdwardsDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Hyunil JoDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA.
Yibing WuDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA.
Daniel DiMaioDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA. daniel.dimaio@yale.edu.ORCID 0000-0002-2060-5977
William F DeGradoDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA. bill.degrado@ucsf.edu.ORCID 0000-0003-4745-263X
University of California, San Francisco · USYale University · USScripps Research Institute · USUniversity of North Carolina at Chapel Hill · USYale Cancer Center · US

Funding

CELL TRANSFORMATION BY BOVINE PAPILLOMAVIRUSR01CA037157 · NCI · YALE UNIVERSITY · PI DIMAIO, DANIEL C. · 1985 to 2019
$9.9M
Proposal for Central California 900 MHZ NMR SpectrometerP41GM068933 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI WEMMER, DAVID E · 2003 to 2007
$5.9M
CELL TRANSFORMATION BY BOVINE PAPILLOMAVIRUSR37CA037157 · NCI · YALE UNIVERSITY · PI DIMAIO, DANIEL · 1992 to 1999
–
NCI NIH HHS R01 CA037157NCI NIH HHS R37 CA037157NIGMS NIH HHS P41 GM068933U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA037157U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM68933U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35-122603
6 · The paper itself

Abstract

Transmembrane (TM) domains as simple as a single span can perform complex biological functions using entirely lipid-embedded chemical features. Computational design has the potential to generate custom tool molecules directly targeting membrane proteins at their functional TM regions. Thus far, designed TM domain-targeting agents have been limited to mimicking the binding modes and motifs of natural TM interaction partners. Here, we demonstrate the design of de novo TM proteins targeting the erythropoietin receptor (EpoR) TM domain in a custom binding topology competitive with receptor homodimerization. The TM proteins expressed in mammalian cells complex with EpoR and inhibit erythropoietin-induced cell proliferation. In vitro, the synthetic TM domain complex outcompetes EpoR homodimerization. Structural characterization reveals that the complex involves the intended amino acids and agrees with our designed molecular model of antiparallel TM helices at 1:1 stoichiometry. Thus, membrane protein TM regions can now be targeted in custom-designed topologies.

Indexed as

Membrane ProteinsProtein BindingReceptors, ErythropoietinAmino Acid SequenceAnimalsCell ProliferationHEK293 CellsHumansModels, MolecularProtein MultimerizationReceptors, CytokineMembrane ProteinsReceptors, CytokineReceptors, Erythropoietin

Identifiers

PMID38480980
PMCPMC11142920
OpenAlexW4392750933

What Socratic holds

Textmetadata
LicenceCC BY
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.