Evidence map›Paper›PMID 35921442›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody.

Bin Xie, Allison Maker, Andrew V Priest, David M Dranow, Jenny N Phan, Thomas E Edwards, Bart L Staker, Peter J Myler, Barry M Gumbiner, Sanjeevi Sivasankar

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.2field-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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  6. Review
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  11. Engineering the Interactions of Classical Cadherin Cell-Cell Adhesion Proteins.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Review
  12. Article
  13. 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

10 authors at 4 institutions in 1 country.

Bin XieBiophysics Graduate Group, University of California, Davis, CA, 95616.ORCID 0000-0002-2305-7865
Allison MakerSeattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, 98101.
Andrew V PriestDepartment of Biomedical Engineering, University of California, Davis, CA, 95616.
David M DranowSeattle Structural Genomics Center for Infectious Disease, Seattle, WA, 98109.
Jenny N PhanSeattle Structural Genomics Center for Infectious Disease, Seattle, WA, 98109.
Thomas E EdwardsSeattle Structural Genomics Center for Infectious Disease, Seattle, WA, 98109.
Bart L StakerSeattle Structural Genomics Center for Infectious Disease, Seattle, WA, 98109.
Peter J MylerSeattle Structural Genomics Center for Infectious Disease, Seattle, WA, 98109.ORCID 0000-0002-0056-0513
Barry M GumbinerSeattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, 98101.
Sanjeevi SivasankarBiophysics Graduate Group, University of California, Davis, CA, 95616.ORCID 0000-0003-2593-0477
UCB Pharma (United States) · USUniversity of California, Davis · USInfectious Disease Research Institute · USUniversity of Washington · US

Funding

Regulation of cell junctions and cell contact dependent signaling in tissue development and physiologyR35GM122467 · NIGMS · SEATTLE CHILDREN'S HOSPITAL · PI GUMBINER, BARRY M. · 2017 to 2021
$3.9M
Mechanosensitive cadherin adhesion and its regulationR01GM133880 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SIVASANKAR, SANJEEVI · 2021 to 2024
$1.5M
HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM133880NIAID NIH HHS HHSN272201700059CNIGMS NIH HHS R01 GM133880NIGMS NIH HHS R35 GM122467
6 · The paper itself

Abstract

E-cadherin (Ecad) is an essential cell-cell adhesion protein with tumor suppression properties. The adhesive state of Ecad can be modified by the monoclonal antibody 19A11, which has potential applications in reducing cancer metastasis. Using X-ray crystallography, we determine the structure of 19A11 Fab bound to Ecad and show that the antibody binds to the first extracellular domain of Ecad near its primary adhesive motif: the strand-swap dimer interface. Molecular dynamics simulations and single-molecule atomic force microscopy demonstrate that 19A11 interacts with Ecad in two distinct modes: one that strengthens the strand-swap dimer and one that does not alter adhesion. We show that adhesion is strengthened by the formation of a salt bridge between 19A11 and Ecad, which in turn stabilizes the swapped β-strand and its complementary binding pocket. Our results identify mechanistic principles for engineering antibodies to enhance Ecad adhesion.

Indexed as

Antibodies, MonoclonalCadherinsCell AdhesionCrystallography, X-RayHumansMicroscopy, Atomic ForceMolecular Dynamics SimulationProtein DomainsAntibodies, MonoclonalCadherins19A11adhesionantibodyE-cadherinstrand–swap dimer

Identifiers

PMID35921442
PMCPMC9371698
OpenAlexW4289637421

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.