ArticleScience advances2021
Structural insights into the mechanism of human NPC1L1-mediated cholesterol uptake.
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 33 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.
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Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- Dual functions of NPC1L1 for cholesterol transport: Cholesterol capture and regulation of inner-leaflet cholesterol accessibility.iScience · 2026Article
- Heat-Inactivated Lactiplantibacillus plantarum H6 Potentiates Low-Dose Simvastatin Efficacy Against Hypercholesterolemia in Mice Through Gut Microbiota Modulation.Probiotics and antimicrobial proteins · 2026Article
- 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
- Identification of gemilukast as a bifunctional molecule with lipid-lowering and anti-inflammatory activities.Frontiers in immunology · 2026Article
- Advanced multifunctional nano-delivery platform focusing on treating diseases related to lipid metabolism via targeted intervention in various lipid metabolic processes.Military Medical Research · 2025Review
- Cassava Fiber Prevents High-Fat Diet-Induced Obesity in Mice Through Gut Microbiota Restructuring.Foods (Basel, Switzerland) · 2025Article
- Biliverdin targeting TcdB-DRBD inhibits Clostridioides difficile virulence and restores gut microbiota in Mongolian gerbils (Meriones unguiculatus).Communications biology · 2025Article
- Pediatric Familial Hypercholesterolemia: Targeting Intestinal Absorption and Other Therapeutic Strategies.Nutrients · 2025Review
- Efficient Hydrolysis of Earthworm Protein and the Lipid-Lowering Mechanism of Peptides in the Hydrolysate.Foods (Basel, Switzerland) · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- Identification of a Novel NPC1L1 Inhibitor from Danshen and Its Role in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2025Article
- Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025Review
- Formulation Strategies for Ezetimibe and Its Combinations: Advancing Biopharmaceutical and Therapeutic Potential.Drug design, development and therapy · 2025Review
- Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins.Frontiers in pharmacology · 2025Review
- Article
- Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis.Neural regeneration research · 2024Article
- Therapeutic Role of Polyphenol Extract fromPlants (Basel, Switzerland) · 2024Article
- NPC1L1 Plays a Novel Role in Nonalcoholic Fatty Liver Disease.ACS omega · 2023Review
- Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.Science (New York, N.Y.) · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Niemann-Pick C1-like 1 (NPC1L1) protein plays a central role in the intestinal cholesterol absorption and is the target of a drug, ezetimibe, which inhibits NPC1L1 to reduce cholesterol absorption. Here, we present cryo-electron microscopy structures of human NPC1L1 in apo state, cholesterol-enriched state, and ezetimibe-bound state to reveal molecular details of NPC1L1-mediated cholesterol uptake and ezetimibe inhibition. Comparison of these structures reveals that the sterol-sensing domain (SSD) could respond to the cholesterol level alteration by binding different number of cholesterol molecules. Upon increasing cholesterol level, SSD binds more cholesterol molecules, which, in turn, triggers the formation of a stable structural cluster in SSD, while binding of ezetimibe causes the deformation of the SSD and destroys the structural cluster, leading to the inhibition of NPC1L1 function. These results provide insights into mechanisms of NPC1L1 function and ezetimibe action and are of great significance for the development of new cholesterol absorption inhibitors.
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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.