Evidence map›Paper›PMID 33775696›Full record

ArticleThe Journal of biological chemistry

Collagen IV

Vadim Pedchenko, Sergei P Boudko, Mary Barber, Tatiana Mikhailova, Juan Saus, Jean-Christophe Harmange, Billy G Hudson

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry. 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
2.0field-weighted citation impact, top 15% 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, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. IncreasedWellcome open research · 2025
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Collagen IVThe Journal of biological chemistry
    Article
  10. Collagen IVThe Journal of biological chemistry
    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 4 institutions in 2 countries.

Vadim PedchenkoDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Sergei P BoudkoDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Biochemistry, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, USA.
Mary BarberAspirnaut, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Tatiana MikhailovaAspirnaut, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Juan SausDepartment de Bioquímica y Biología Molecular at Facultad de Medicina y Odontología, University de València, Valencia, Spain.
Jean-Christophe HarmangeGoldfinch Bio, Cambridge, Massachusetts, USA.
Billy G HudsonDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Biochemistry, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, USA; Aspirnaut, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, USA. Electronic address: billy.hudson@vumc.org.
Vanderbilt University Medical Center · USVanderbilt University · USGoldfinch Bio (United States) · USUniversitat de València · ES

Funding

STUDIES ON THE STRUCTURE OF BASEMENT MEMBRANESR01DK018381 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Sergey Petrovich Budko, BILLY GERALD HUDSON · 1986 to 2026
$12.4M
Novel Integrated Analyses of Human Diabetic NephropathyR24DK103067 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CAPRIOLI, RICHARD M, DENNY, JOSHUA C. · 2014 to 2018
$6.5M
Glucose Modifications of Proteins in Diabetic NephropathyR01DK065138 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HUDSON, BILLY GERALD, VOZIYAN, PAUL A · 2003 to 2020
$6.3M
Undergraduate Research Internships in Pathobiology of Diabetic NephropathyR25DK096999 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BILLY GERALD HUDSON · 2012 to 2026
$1.6M
NIDDK NIH HHS R01 DK018381NIDDK NIH HHS R01 DK065138NIDDK NIH HHS R24 DK103067NIDDK NIH HHS R25 DK096999
6 · The paper itself

Abstract

We identified a genetic variant, an 8-residue appendage, of the α345 hexamer of collagen IV present in patients with glomerular basement membrane diseases, Goodpasture's disease and Alport syndrome, and determined the long-awaited crystal structure of the hexamer. We sought to elucidate how variants cause glomerular basement membrane disease by exploring the mechanism of the hexamer assembly. Chloride ions induced in vitro hexamer assembly in a composition-specific manner in the presence of equimolar concentrations of α3, α4, and α5 NC1 monomers. Chloride ions, together with sulfilimine crosslinks, stabilized the assembled hexamer. Furthermore, the chloride ion-dependent assembly revealed the conformational plasticity of the loop-crevice-loop bioactive sites, a critical property underlying bioactivity and pathogenesis. We explored the native mechanism by expressing recombinant α345 miniprotomers in the cell culture and characterizing the expressed proteins. Our findings revealed NC1-directed trimerization, forming protomers inside the cell; hexamerization, forming scaffolds outside the cell; and a Cl gradient-signaled hexamerization. This assembly detail, along with a crystal structure, provides a framework for understanding hexamer dysfunction. Restoration of the native conformation of bioactive sites and α345 hexamer replacement are prospective approaches to therapeutic intervention.

Indexed as

MutationProtein MultimerizationAnti-Glomerular Basement Membrane DiseaseCell LineCollagen Type IVNephritis, HereditaryProtein Structure, QuaternaryCollagen Type IV

Identifiers

PMID33775696
PMCPMC8099640
OpenAlexW3136269923

What OpenQuestion holds

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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.