ArticleThe Journal of biological chemistry2015
Multiple Surface Regions on the Niemann-Pick C2 Protein Facilitate Intracellular Cholesterol Transport.
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 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Genome of the invasive North American Haemaphysalis longicornis tick as a template for bovine anti-tick vaccine discovery.BMC genomics · 2025Article
- Role of lipid binding protein, Niemann pick type C-2, in enhancing shrimp sperm physiological function.Heliyon · 2025Article
- Deficiency in NPC2 results in disruption of mitochondria-late endosome/lysosomes contact sites and endo-lysosomal lipid dyshomeostasis.Scientific reports · 2025Article
- Structural and biochemical analysis of ligand binding in yeast Niemann-Pick type C1-related protein.Life science alliance · 2025Article
- Molecular determinants of phospholipid treatment to reduce intracellular cholesterol accumulation in NPC1 deficiency.The Journal of biological chemistry · 2024Article
- The Cerebellum in Niemann-Pick C1 Disease: Mouse Versus Man.Cerebellum (London, England) · 2023Review
- Alterations in Cholesterol and Phosphoinositides Levels in the Intracellular Cholesterol Trafficking Disorder NPC.Advances in experimental medicine and biology · 2023Article
- Involvement of the Choroid Plexus in the Pathogenesis of Niemann-Pick Disease Type C.Frontiers in cellular neuroscience · 2021Article
- Fbxo2 mediates clearance of damaged lysosomes and modifies neurodegeneration in the Niemann-Pick C brain.JCI insight · 2020Article
- Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid.eLife · 2019Article
- Article
- NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes.The Journal of biological chemistry · 2019Review
- Nonphotodynamic Roles of Methylene Blue: Display of Distinct Antimycobacterial and Anticandidal Mode of Actions.Journal of pathogens · 2018Article
- A molecular signature of lung cancer: potential biomarkers for adenocarcinoma and squamous cell carcinoma.Oncotarget · 2017Article
- Emerging Roles for the Lysosome in Lipid Metabolism.Trends in cell biology · 2017Review
- Concerted regulation of npc2 binding to endosomal/lysosomal membranes by bis(monoacylglycero)phosphate and sphingomyelin.PLoS computational biology · 2017Article
- Article
- EhNPC1 and EhNPC2 Proteins Participate in Trafficking of Exogenous Cholesterol in Entamoeba histolytica Trophozoites: Relevance for Phagocytosis.PLoS pathogens · 2016Article
- Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The cholesterol storage disorder Niemann-Pick type C (NPC) disease is caused by defects in either of two late endosomal/lysosomal proteins, NPC1 and NPC2. NPC2 is a 16-kDa soluble protein that binds cholesterol in a 1:1 stoichiometry and can transfer cholesterol between membranes by a mechanism that involves protein-membrane interactions. To examine the structural basis of NPC2 function in cholesterol trafficking, a series of point mutations were generated across the surface of the protein. Several NPC2 mutants exhibited deficient sterol transport properties in a set of fluorescence-based assays. Notably, these mutants were also unable to promote egress of accumulated intracellular cholesterol from npc2(-/-) fibroblasts. The mutations mapped to several regions on the protein surface, suggesting that NPC2 can bind to more than one membrane simultaneously. Indeed, we have previously demonstrated that WT NPC2 promotes vesicle-vesicle interactions. These interactions were abrogated, however, by mutations causing defective sterol transfer properties. Molecular modeling shows that NPC2 is highly plastic, with several intense positively charged regions across the surface that could interact favorably with negatively charged membrane phospholipids. The point mutations generated in this study caused changes in NPC2 surface charge distribution with minimal conformational changes. The plasticity, coupled with membrane flexibility, probably allows for multiple cholesterol transfer routes. Thus, we hypothesize that, in part, NPC2 rapidly traffics cholesterol between closely appositioned membranes within the multilamellar interior of late endosomal/lysosomal proteins, ultimately effecting cholesterol egress from this compartment.
Indexed as
Identifiers
What OpenQuestion holds
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.