ArticleScience advances2021
Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Niemann-Pick C1-Like 1 in Cholesterol Absorption and Homeostasis: Mechanisms, Regulation, and Emerging Phytochemical Inhibitors.Current issues in molecular biology · 2026Review
- Ergosterol as a natural modulator of intestinal cholesterol absorption via NPC1L1: anFrontiers in bioinformatics · 2026Article
- Pediatric Familial Hypercholesterolemia: Targeting Intestinal Absorption and Other Therapeutic Strategies.Nutrients · 2025Review
- Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025Review
- Flotillins in membrane trafficking and physiopathology.Biology of the cell · 2025Review
- Potential function of hepatic Niemann-Pick C1-like 1: cholesterol homeostasis regulation of the canalicular lipid bilayer membrane.Gastroenterology report · 2025Review
- Repositioning of ezetimibe for the treatment of idiopathic pulmonary fibrosis.The European respiratory journal · 2024Article
- Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.Science (New York, N.Y.) · 2023Article
- RNA-Seq analysis of the pyloric caecum, liver, and muscle reveals molecular mechanisms regulating fillet color in rainbow trout.BMC genomics · 2023Article
- Unraveling a mystery: Why human cells require cholesterol.Science advances · 2022Review
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- Lowering low-density lipoprotein cholesterol: from mechanisms to therapies.Life metabolism · 2022Review
- Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain.Nature communications · 2022Article
- Peroxisome Proliferator-Activated Receptor-α: A Pivotal Regulator of the Gastrointestinal Tract.Frontiers in molecular biosciences · 2022Review
- Progress of potential drugs targeted in lipid metabolism research.Frontiers in pharmacology · 2022Review
- The role of NPC1L1 in cancer.Frontiers in pharmacology · 2022Review
- Cholesterol efflux mechanism revealed by structural analysis of human ABCA1 conformational states.Nature cardiovascular research · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Polytopic Niemann-Pick C1-like 1 (NPC1L1) plays a major role in intestinal absorption of biliary cholesterol, vitamin E (VE), and vitamin K (VK). The drug ezetimibe inhibits NPC1L1-mediated absorption of cholesterol, lowering of circulating levels of low-density lipoprotein cholesterol. Here, we report cryo-electron microscopy structures of human NPC1L1 (hNPC1L1) bound to either cholesterol or a lipid resembling VE. These findings, together with functional assays, reveal that the same intramolecular channel in hNPC1L1 mediates transport of VE and cholesterol. hNPC1L1 exists primarily as a homodimer; dimerization is mediated by aromatic residues within a region of transmembrane helix 2 that exhibits a horizonal orientation in the membrane. Mutation of tryptophan-347 lies in this region disrupts dimerization and the resultant monomeric NPC1L1 exhibits reduced efficiency of cholesterol uptake. These findings identify the oligomeric state of hNPC1L1 as a target for therapies that inhibit uptake of dietary cholesterol and reduce the incidence of cardiovascular disease.
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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.