Evidence map›Paper›PMID 29915162›Full record

ArticleThe Journal of general physiology2018

Molecular determination of claudin-15 organization and channel selectivity.

Priyanka Samanta, Yitang Wang, Shadi Fuladi, Jinjing Zou, Ye Li, Le Shen, Christopher Weber, Fatemeh Khalili-Araghi

Abstract read
In one paragraph

Article in The Journal of general physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Article
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  7. Ion and water permeation through claudin-10b and claudin-15 paracellular channels.Computational and structural biotechnology journal · 2024
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Priyanka SamantaDepartment of Physics, University of Illinois, Chicago, IL.ORCID 0000-0003-1922-1885
Yitang WangDepartment of Pathology, The University of Chicago, Chicago, IL.
Shadi FuladiDepartment of Physics, University of Illinois, Chicago, IL.
Jinjing ZouDepartment of Pathology, The University of Chicago, Chicago, IL.
Ye LiDepartment of Pathology, The University of Chicago, Chicago, IL.ORCID 0000-0002-2969-2894
Le ShenDepartment of Pathology, The University of Chicago, Chicago, IL leshen@uchicago.edu.ORCID 0000-0002-4367-5476
Christopher WeberDepartment of Pathology, The University of Chicago, Chicago, IL christopher.weber@uchospitals.edu.ORCID 0000-0002-2117-3184
Fatemeh Khalili-AraghiDepartment of Physics, University of Illinois, Chicago, IL akhalili@uic.edu.

Funding

ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI LIU, CAMBRIAN YANGSHAO · 1990 to 2025
$29.8M
Contribution of occludin to intestinal homeostasis and diseaseK01DK092381 · NIDDK · UNIVERSITY OF CHICAGO · PI SHEN, LE · 2012 to 2016
$751k
Mechanisms and pathways of trans-tight junction conductanceK08DK088953 · NIDDK · UNIVERSITY OF CHICAGO · PI WEBER, CHRISTOPHER · 2010 to 2014
$733k
NIDDK NIH HHS K01 DK092381NIDDK NIH HHS K08 DK088953
6 · The paper itself

Abstract

Tight junctions are macromolecular structures that traverse the space between adjacent cells in epithelia and endothelia. Members of the claudin family are known to determine tight junction permeability in a charge- and size-selective manner. Here, we use molecular dynamics simulations to build and refine an atomic model of claudin-15 channels and study its transport properties. Our simulations indicate that claudin-15 forms well-defined channels for ions and molecules and otherwise "seals" the paracellular space through hydrophobic interactions. Ionic currents, calculated from simulation trajectories of wild-type as well as mutant channels, reflect in vitro measurements. The simulations suggest that the selectivity filter is formed by a cage of four aspartic acid residues (D55), contributed by four claudin-15 molecules, which creates a negative electrostatic potential to favor cation flux over anion flux. Charge reversal or charge ablation mutations of D55 significantly reduce cation permeability in silico and in vitro, whereas mutations of other negatively charged pore amino acid residues have a significantly smaller impact on channel permeability and selectivity. The simulations also indicate that water and small ions can pass through the channel, but larger cations, such as tetramethylammonium, do not traverse the pore. Thus, our model provides an atomic view of claudin channels, their transport function, and a potential three-dimensional organization of its selectivity filter.

Indexed as

Molecular Dynamics SimulationAnimalsBinding SitesClaudinsIon TransportMiceclaudin 15Claudins

Identifiers

PMID29915162
PMCPMC6028499

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LicenceCC BY-NC-SA
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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.