Evidence map›Paper›PMID 38886509›Full record

ArticleCommunications biology2024

Structural and biophysical insights into targeting of claudin-4 by a synthetic antibody fragment.

Satchal K Erramilli, Pawel K Dominik, Chinemerem P Ogbu, Anthony A Kossiakoff, Alex J Vecchio

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. CK8/18 and Claudin Profile of Female Breast Cancers from Botswana.Breast cancer : basic and clinical research · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Computational and structural biotechnology journal · 2025
    Article
  10. Review
  11. Article
  12. Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  13. Article
  14. 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

5 authors.

Satchal K ErramilliDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.
Pawel K DominikDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.
Chinemerem P OgbuDepartment of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.ORCID 0000-0001-5663-7148
Anthony A KossiakoffDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.ORCID 0000-0003-3174-9359
Alex J VecchioDepartment of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA. vecchioa@buffalo.edu.ORCID 0000-0002-4222-7874

Funding

Pacific Northwest Center for Cryo-EM - Screening supplementU24GM129547 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI EVANS, JAMES E, GOUAUX, JAMES E · 2018 to 2023
$54.8M
Chaperone-Assisted Structure Determination of Membrane ProteinsR01GM117372 · NIGMS · UNIVERSITY OF CHICAGO · PI ANTHONY A KOSSIAKOFF · 2016 to 2026
$4.0M
Structure and Assembly of Membrane Proteins at Tight JunctionsR35GM138368 · NIGMS · UNIVERSITY OF NEBRASKA LINCOLN · PI Alex J. Vecchio · 2020 to 2026
$3.1M
National Science Foundation (NSF) OIA-2131902NIGMS NIH HHS R01 GM117372NIGMS NIH HHS R35 GM138368NIGMS NIH HHS U24 GM129547U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM117372U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM138368
6 · The paper itself

Abstract

Claudins are a 27-member family of ~25 kDa membrane proteins that integrate into tight junctions to form molecular barriers at the paracellular spaces between endothelial and epithelial cells. As the backbone of tight junction structure and function, claudins are attractive targets for modulating tissue permeability to deliver drugs or treat disease. However, structures of claudins are limited due to their small sizes and physicochemical properties-these traits also make therapy development a challenge. Here we report the development of a synthetic antibody fragment (sFab) that binds human claudin-4 and the determination of a high-resolution structure of it bound to claudin-4/enterotoxin complexes using cryogenic electron microscopy. Structural and biophysical results reveal this sFabs mechanism of select binding to human claudin-4 over other homologous claudins and establish the ability of sFabs to bind hard-to-target claudins to probe tight junction structure and function. The findings provide a framework for tight junction modulation by sFabs for tissue-selective therapies.

Indexed as

Claudin-4Cryoelectron MicroscopyEnterotoxinsHumansImmunoglobulin FragmentsModels, MolecularProtein BindingTight JunctionsClaudin-4CLDN4 protein, humanenterotoxin, ClostridiumEnterotoxinsImmunoglobulin Fragments

Identifiers

PMID38886509
PMCPMC11183071

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Registered trials

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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.