Evidence map›Paper›PMID 26032415›Full record

ArticleThe Journal of biological chemistry2015

The Cholesterol-dependent Cytolysin Membrane-binding Interface Discriminates Lipid Environments of Cholesterol to Support β-Barrel Pore Insertion.

Allison J Farrand, Eileen M Hotze, Takehiro K Sato, Kristin R Wade, William C Wimley, Arthur E Johnson, Rodney K Tweten

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

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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.

Allison J FarrandDepartment of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
Eileen M HotzeDepartment of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
Takehiro K SatoDepartments of Molecular and Cellular Medicine, Texas A&M University, College Station, Texas 77843.
Kristin R WadeDepartment of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
William C WimleyDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Arthur E JohnsonDepartments of Molecular and Cellular Medicine, Texas A&M University, College Station, Texas 77843; Departments of Chemistry and Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843.
Rodney K TwetenDepartment of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104. Electronic address: Rod-Tweten@ouhsc.edu.

Funding

Pore Formation by Cholesterol Dependent CytolysinsR01AI037657 · NIAID · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI TWETEN, RODNEY K. · 1997 to 2015
$5.4M
NIAID NIH HHS AI037657NIAID NIH HHS R01 AI037657
6 · The paper itself

Abstract

The majority of cholesterol-dependent cytolysins (CDCs) utilize cholesterol as a membrane receptor, whereas a small number are restricted to the GPI-anchored protein CD59 for initial membrane recognition. Two cholesterol-binding CDCs, perfringolysin O (PFO) and streptolysin O (SLO), were found to exhibit strikingly different binding properties to cholesterol-rich natural and synthetic membranes. The structural basis for this difference was mapped to one of the loops (L3) in the membrane binding interface that help anchor the toxin monomers to the membrane after receptor (cholesterol) binding by the membrane insertion of its amino acid side chains. A single point mutation in this loop conferred the binding properties of SLO to PFO and vice versa. Our studies strongly suggest that changing the side chain structure of this loop alters its equilibrium between membrane-inserted and uninserted states, thereby affecting the overall binding affinity and total bound toxin. Previous studies have shown that the lipid environment of cholesterol has a dramatic effect on binding and activity. Combining this data with the results of our current studies on L3 suggests that the structure of this loop has evolved in the different CDCs to preferentially direct binding to cholesterol in different lipid environments. Finally, the efficiency of β-barrel pore formation was inversely correlated with the increased binding and affinity of the PFO L3 mutant, suggesting that selection of a compatible lipid environment impacts the efficiency of membrane insertion of the β-barrel pore.

Indexed as

Bacterial Physiological PhenomenaAmino Acid SequenceAnimalsBacterial ProteinsBacterial ToxinsCell LineCell MembraneCholesterolCytotoxinsHemolysin ProteinsLiposomesMiceModels, MolecularProtein BindingProtein Structure, SecondaryStreptolysinsBacterial ProteinsBacterial ToxinsCholesterolClostridium perfringens theta-toxinCytotoxinsHemolysin ProteinsLiposomesstreptolysin OStreptolysinsbacterial toxincholesterollipid structuremembrane lipidmembrane structure

Identifiers

PMID26032415
PMCPMC4505022

What OpenQuestion holds

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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.