Evidence map›Paper›PMID 38308046›Full record

ArticleNature chemical biology2024

Antibody discovery identifies regulatory mechanisms of protein arginine deiminase 4.

Xin Zhou, Sophie Kong, Allison Maker, Soumya G Remesh, Kevin K Leung, Kliment A Verba, James A Wells

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 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
9.3field-weighted citation impact, top 2% 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

10 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Glycosaminoglycans activate peptidylarginine deiminase 4 by enhancing calcium affinity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Citrullination in tumor immunity and therapy.The Journal of clinical investigation · 2025
    Review
  8. Review
  9. Structural insight into the function of human peptidyl arginine deiminase 6.Computational and structural biotechnology journal · 2024
    Article
  10. 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

7 authors at 2 institutions in 1 country.

Xin Zhou *Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8198-2856
Sophie Kong *Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Allison MakerDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
Soumya G RemeshDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Kevin K LeungDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2087-4974
Kliment A VerbaDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2238-8590
James A WellsDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA. jim.wells@ucsf.edu.ORCID 0000-0001-8267-5519
University of California, San Francisco · USHarvard University · US

Funding

MOLECULAR AND CELLULAR BASIS OF CARDIOVASCULAR DISEASET32HL007731 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian L Black · 1992 to 2026
$12.4M
Affinity-directed tagging of protein binding partners in signalingR01CA191018 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2014 to 2018
$1.6M
Regulating Proteolysis to Dissect ApoptosisR01GM097316 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2011 to 2014
$1.1M
Interrogating and rewiring cell signaling pathways in CAR-T cells with synthetic phosphotyrosine recognition domainsR00EB030587 · NIBIB · DANA-FARBER CANCER INST · PI ZHOU, XIN · 2022 to 2024
$733k
Interrogating and rewiring cell signaling pathways in CAR-T cells with synthetic phosphotyrosine recognition domainsK99EB030587 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZHOU, XIN · 2020 to 2021
$174k
Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) (DFS-52-22Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) DRG-665 2297-17NCI NIH HHS R01 CA191018NIBIB NIH HHS K99 EB030587NIBIB NIH HHS R00 EB030587NIGMS NIH HHS R01 GM097316U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM097316U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1P41CA1962 76U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA191018U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) K99EB030587U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) R00EB030587
6 · The paper itself

Abstract

Unlocking the potential of protein arginine deiminase 4 (PAD4) as a drug target for rheumatoid arthritis requires a deeper understanding of its regulation. In this study, we use unbiased antibody selections to identify functional antibodies capable of either activating or inhibiting PAD4 activity. Through cryogenic-electron microscopy, we characterized the structures of these antibodies in complex with PAD4 and revealed insights into their mechanisms of action. Rather than steric occlusion of the substrate-binding catalytic pocket, the antibodies modulate PAD4 activity through interactions with allosteric binding sites adjacent to the catalytic pocket. These binding events lead to either alteration of the active site conformation or the enzyme oligomeric state, resulting in modulation of PAD4 activity. Our study uses antibody engineering to reveal new mechanisms for enzyme regulation and highlights the potential of using PAD4 agonist and antagonist antibodies for studying PAD4-dependency in disease models and future therapeutic development.

Indexed as

Protein-Arginine Deiminase Type 4AntibodiesArthritis, RheumatoidCatalytic DomainCryoelectron MicroscopyHumansHydrolasesModels, MolecularProtein-Arginine DeiminasesAntibodiesHydrolasesPADI4 protein, humanProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4

Identifiers

PMID38308046
PMCPMC11142921
OpenAlexW4391474842

What OpenQuestion 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 OpenQuestion graph.