Evidence map›Paper›PMID 30923125›Full record

ArticleThe Journal of biological chemistry2019

A chloride ring is an ancient evolutionary innovation mediating the assembly of the collagen IV scaffold of basement membranes.

Vadim Pedchenko, Ryan Bauer, Elena N Pokidysheva, Alaa Al-Shaer, Nancy R Forde, Aaron L Fidler, Billy G Hudson, Sergei P Boudko

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Review
  6. Review
  7. The life cycle of type IV collagen.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Review
  8. Article
  9. Decoding collagen's thermally induced unfolding and refolding pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. The Link between Oxygen and Basement Membranes.Reviews of physiology, biochemistry and pharmacology · 2025
    Review
  11. Article
  12. Collagen IV Exploits a Cl- Step Gradient for Scaffold Assembly.Advances in experimental medicine and biology · 2021
    Review
  13. ClAmerican journal of physiology. Cell physiology · 2020
    Review
  14. Collagen IVThe Journal of biological chemistry
    Article
  15. 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

8 authors at 3 institutions in 2 countries.

Vadim PedchenkoDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Ryan BauerDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Elena N PokidyshevaDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Alaa Al-ShaerDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Nancy R FordeDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada; Department of Physics, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Aaron L FidlerDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Department of AspirnautTM Program, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Billy G HudsonDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Department of AspirnautTM Program, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232; Department of Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232; Department of Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232.
Sergei P BoudkoDepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232. Electronic address: sergey.budko@vanderbilt.edu.
Vanderbilt University Medical Center · USSimon Fraser University · CAVanderbilt University · US

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
VANDERBILT NEPHROLOGY TRAINING PROGRAMT32DK007569 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HARRIS, RAYMOND C., IKIZLER, TALAT ALP · 1988 to 2024
$5.8M
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 R25 DK096999NIDDK NIH HHS T32 DK007569
6 · The paper itself

Abstract

Collagen IV scaffold is a principal component of the basement membrane (BM), a specialized extracellular matrix that is essential for animal multicellularity and tissue evolution. Scaffold assembly begins with the trimerization of α-chains into protomers inside the cell, which then are secreted and undergo oligomerization outside the cell. For the ubiquitous scaffold composed of α1- and α2-chains, both intracellular and extracellular stages are mediated by the noncollagenous domain (NC1). The association of protomers is chloride-dependent, whereby chloride ions induce interactions of the protomers' trimeric NC1 domains leading to NC1 hexamer formation. Here, we investigated the mechanisms, kinetics, and functionality of the chloride ion-mediated protomer assembly by using a single-chain technology to produce a stable NC1 trimer comprising α1, α2, and α1 NC1 monomers. We observed that in the presence of chloride, the single-chain NC1-trimer self-assembles into a hexamer, for which the crystal structure was determined. We discovered that a chloride ring, comprising 12 ions, induces the assembly of and stabilizes the NC1 hexamer. Furthermore, we found that the chloride ring is evolutionarily conserved across all animals, first appearing in cnidarians. These findings reveal a fundamental role for the chloride ring in the assembly of collagen IV scaffolds of BMs, a critical event enabling tissue evolution and development. Moreover, the single-chain technology is foundational for generating trimeric NC1 domains of other α-chain compositions to investigate the α121, α345, and α565 collagen IV scaffolds and to develop therapies for managing Alport syndrome, Goodpasture's disease, and cancerous tumor growth.

Indexed as

Models, MolecularCollagen Type IVCrystallography, X-RayHumansProtein Structure, QuaternaryProtein Structure, TertiaryCollagen Type IVanimal evolutionbasement membranechloridecollagencollagen IVconnective tissuecrystal structureECMextracellular matrixkineticsNC1 domainprotein self-assembly

Identifiers

PMID30923125
PMCPMC6527180
OpenAlexW2934758797

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.