Evidence map›Paper›PMID 27720987›Full record

ArticleJournal of molecular biology2016

Death Receptor 5 Networks Require Membrane Cholesterol for Proper Structure and Function.

Andrew K Lewis, Christopher C Valley, Stephen L Peery, Benjamin Brummel, Anthony R Braun, Christine B Karim, Jonathan N Sachs

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Conformational states of TNFR1 as a molecular switch for receptor function.Protein science : a publication of the Protein Society · 2020
    Article
  6. Article
  7. Fast-diffusing p75Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  8. Article
  9. Article
  10. Solid-State NMR of highlyMethods (San Diego, Calif.) · 2018
    Article
  11. Review
  12. 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 1 institution in 1 country.

Andrew K LewisDepartment of Biomedical Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
Christopher C ValleyDepartment of Biomedical Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
Stephen L PeeryDepartment of Biomedical Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
Benjamin BrummelDepartment of Biomedical Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
Anthony R BraunDepartment of Biomedical Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
Christine B KarimDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
Jonathan N SachsDepartment of Biomedical Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA. Electronic address: jnsachs@umn.edu.
University of Minnesota · US

Funding

Dynamics of transmembrane dimers in TNF-Receptors by EPR and molecular simulationR01GM107175 · NIGMS · UNIVERSITY OF MINNESOTA · PI SACHS, JONATHAN N · 2014 to 2017
$1.3M
NIGMS NIH HHS R01 GM107175
6 · The paper itself

Abstract

Death receptor 5 (DR5) is an apoptosis-inducing member of the tumor necrosis factor receptor superfamily, whose activity has been linked to membrane cholesterol content. Upon ligand binding, DR5 forms large clusters within the plasma membrane that have often been assumed to be manifestations of receptor co-localization in cholesterol-rich membrane domains. However, we have recently shown that DR5 clusters are more than just randomly aggregated receptors. Instead, these are highly structured networks held together by receptor dimers. These dimers are stabilized by specific transmembrane helix-helix interactions, including a disulfide bond in the long isoform of the receptor. The complex relationships among DR5 network formation, transmembrane helix dimerization, membrane cholesterol, and receptor activity has not been established. It is unknown whether the membrane itself plays an active role in driving DR5 transmembrane helix interactions or in the formation of the networks. We show that cholesterol depletion in cells does not inhibit the formation of DR5 networks. However, the networks that form in cholesterol-depleted cells fail to induce caspase cleavage. These results suggest a potential structural difference between active and inactive networks. As evidence, we show that cholesterol is necessary for the covalent dimerization of DR5 transmembrane domains. Molecular simulations and experiments in synthetic vesicles on the DR5 transmembrane dimer suggest that dimerization is facilitated by increased helicity in a thicker bilayer.

Indexed as

Protein MultimerizationCaspasesCholesterolHumansJurkat CellsMembrane LipidsModels, BiologicalProtein ConformationProteolysisReceptors, TNF-Related Apoptosis-Inducing LigandCaspasesCholesterolMembrane LipidsReceptors, TNF-Related Apoptosis-Inducing Ligandcholesterol-rich membrane domainsdisulfide bondligand/receptor clusteringreplica exchange molecular dynamicstransmembrane domain

Identifiers

PMID27720987
PMCPMC5394796
OpenAlexW2531554456

What OpenQuestion holds

Textmetadata
LicenceTDM
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.