ArticleJournal of molecular biology2016
Death Receptor 5 Networks Require Membrane Cholesterol for Proper Structure and Function.
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.
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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.
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.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Nimesulide, a COX-2 inhibitor, sensitizes pancreatic cancer cells to TRAIL-induced apoptosis by promoting DR5 clustering †.Cancer biology & therapy · 2023Article
- Alteration of cholesterol distribution at the plasma membrane of cancer cells: From evidence to pathophysiological implication and promising therapy strategy.Frontiers in physiology · 2022Review
- Noncompetitive Allosteric Antagonism of Death Receptor 5 by a Synthetic Affibody Ligand.Biochemistry · 2020Article
- Conformational states of TNFR1 as a molecular switch for receptor function.Protein science : a publication of the Protein Society · 2020Article
- Cholesterol restricts lymphotoxin β receptor-triggered NF-κB signaling.Cell communication and signaling : CCS · 2019Article
- Fast-diffusing p75Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Noncompetitive inhibitors of TNFR1 probe conformational activation states.Science signaling · 2019Article
- Cholesterol Sulfotransferase SULT2B1b Modulates Sensitivity to Death Receptor Ligand TNFα in Castration-Resistant Prostate Cancer.Molecular cancer research : MCR · 2019Article
- Solid-State NMR of highlyMethods (San Diego, Calif.) · 2018Article
- Piecing it together: Unraveling the elusive structure-function relationship in single-pass membrane receptors.Biochimica et biophysica acta. Biomembranes · 2017Review
- Death Receptor 5 Activation Is Energetically Coupled to Opening of the Transmembrane Domain Dimer.Biophysical journal · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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.