ArticleProceedings of the National Academy of Sciences of the United States of America2016
Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 183 citations in OpenAlex.
- Palmitoyltransferase DHHC13 controls lysosomal cholesterol egress through palmitoylating Niemann-Pick C1.Life metabolism · 2026Article
- Mechanistic Basis of Cholesterol Binding and Transfer in NPC2: Insights From Molecular Dynamics Simulations.Chembiochem : a European journal of chemical biology · 2026Article
- Ectopic FGFR1 Increases Intracellular Pool of Cholesterol in Prostate Cancer Cells.International journal of molecular sciences · 2026Article
- Lipid ciliology: specialized ciliary membrane lipids in physiology and disease.Frontiers in cell and developmental biology · 2026Review
- NPC1 trafficking via VPS41-dependent LAMP carriers regulates endosomal cholesterol homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibition of NPC Intracellular Cholesterol Transporter 1 Dually Regulates Aldosterone Secretion Via the Steroidogenic Acute Regulatory-Related Lipid Transfer Domain-3-Voltage-Dependent Anion Channel 1 Axis and Inositol 1,4,5-Trisphosphate Receptor Type 3-Calcium Signaling.Journal of the American Heart Association · 2025Article
- Advances in mass spectrometry of lipids for the investigation of Niemann-pick type C disease.Lipids in health and disease · 2025Review
- Article
- Exploration of Bromodomain Proteins as Drug Targets for Niemann-Pick Type C Disease.International journal of molecular sciences · 2025Article
- Niemann Pick C1 mistargeting disrupts lysosomal cholesterol homeostasis contributing to neurodegeneration in a Batten disease model.Science advances · 2025Article
- Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning.Cell host & microbe · 2025Article
- Endothelial and neuronal engagement by AAV-BR1 gene therapy alleviates neurological symptoms and lipid deposition in a mouse model of Niemann-Pick type C2.Fluids and barriers of the CNS · 2025Article
- Deficiency in NPC2 results in disruption of mitochondria-late endosome/lysosomes contact sites and endo-lysosomal lipid dyshomeostasis.Scientific reports · 2025Article
- Arimoclomol and levacetylleucine for the treatment of neurologic manifestations of Niemann-Pick disease type C: A therapeutics bulletin of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine open · 2025Article
- Unifying biology of neurodegeneration in lysosomal storage diseases.Journal of inherited metabolic disease · 2025Review
- Unbiased MD simulations identify lipid binding sites in lipid transfer proteins.The Journal of cell biology · 2024Article
- NPC1 links cholesterol trafficking to microglial morphology via the gastrosome.Nature communications · 2024Article
- The Aging Lacrimal Gland of Female C57BL/6J Mice Exhibits Multinucleate Macrophage Infiltration Associated With Lipid Dysregulation.Investigative ophthalmology & visual science · 2024Article
- Niemann-Pick Type C2 Proteins inInternational journal of molecular sciences · 2024Article
- Nonsynonymous Mutations in Intellectual Disability and Autism Spectrum Disorder Gene PTCHD1 DisruptCells · 2024Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Export of LDL-derived cholesterol from lysosomes requires the cooperation of the integral membrane protein Niemann-Pick C1 (NPC1) and a soluble protein, Niemann-Pick C2 (NPC2). Mutations in the genes encoding these proteins lead to Niemann-Pick disease type C (NPC). NPC2 binds to NPC1's second (middle), lumenally oriented domain (MLD) and transfers cholesterol to NPC1's N-terminal domain (NTD). Here, we report the 2.4-Å resolution crystal structure of a complex of human NPC1-MLD and NPC2 bearing bound cholesterol-3-O-sulfate. NPC1-MLD uses two protruding loops to bind NPC2, analogous to its interaction with the primed Ebola virus glycoprotein. Docking of the NPC1-NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tunnel between NPC2 and NTD cholesterol binding pockets, supporting the "hydrophobic hand-off" cholesterol transfer model.
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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.