ArticleThe Journal of biological chemistry2017
A retractable lid in lecithin:cholesterol acyltransferase provides a structural mechanism for activation by apolipoprotein A-I.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- A systematic review of the natural history and biomarkers of primary lecithin:cholesterol acyltransferase deficiency.Journal of lipid research · 2022Pooled it
- Lecithin:cholesterol acyltransferase binds a discontinuous binding site on adjacent apolipoprotein A-I belts in HDL.Journal of lipid research · 2025Article
- Understanding the heterogeneity and dysfunction of HDL in chronic kidney disease: insights from recent reviews.BMC nephrology · 2024Review
- Gliflozins, sucrose and flavonoids are allosteric activators of lecithin-cholesterol acyltransferase.Scientific reports · 2024Article
- Rescue of Familial Lecithin:Cholesterol Acyltranferase Deficiency Mutations with an Allosteric Activator.Molecular pharmacology · 2024Article
- Systematic evaluation of lecithin:cholesterol acyltransferase binding sites in apolipoproteins via peptide based nanodiscs: regulatory role of charged residues at positions 4 and 7.PLoS computational biology · 2024Article
- Converting the E. coli Isochorismatase Nicotinamidase into γ-Lactamase.Microbiology spectrum · 2022Article
- Pathways and Mechanisms of Cellular Cholesterol Efflux-Insight From Imaging.Frontiers in cell and developmental biology · 2022Review
- Influence of lecithin cholesterol acyltransferase alteration during different pathophysiologic conditions: A 45 years bibliometrics analysis.Frontiers in pharmacology · 2022Article
- Acyl-CoA-dependent and acyl-CoA-independent avocado acyltransferases positively influence oleic acid content in nonseed triacylglycerols.Frontiers in plant science · 2022Article
- Positive allosteric modulators of lecithin: Cholesterol acyltransferase adjust the orientation of the membrane-binding domain and alter its spatial free energy profile.PLoS computational biology · 2021Article
- rHDL modeling and the anchoring mechanism of LCAT activation.Journal of lipid research · 2021Article
- Single nucleotide polymorphisms in LCAT may contribute to dyslipidaemia in HIV-infected individuals on HAART in a Ghanaian population.Scientific reports · 2020Article
- Metabolic Profiling of Plasma in Different Calving Body Condition Score Cows Using an Untargeted Liquid Chromatography-Mass Spectrometry Metabolomics Approach.Animals : an open access journal from MDPI · 2020Article
- Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings.Journal of lipid research · 2020Article
- Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles.Communications biology · 2020Article
- Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia.Lipids in health and disease · 2019Article
- Plasma lipoprotein-X quantification on filipin-stained gels: monitoring recombinant LCAT treatment ex vivo.Journal of lipid research · 2019Article
- Structural Basis of Lysosomal Phospholipase ABiochemistry · 2019Article
- LCAT Enzyme Replacement Therapy Reduces LpX and Improves Kidney Function in a Mouse Model of Familial LCAT Deficiency.The Journal of pharmacology and experimental therapeutics · 2019Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport by transferring an acyl group from phosphatidylcholine to cholesterol, promoting the maturation of high-density lipoproteins (HDL) from discoidal to spherical particles. LCAT is activated through an unknown mechanism by apolipoprotein A-I (apoA-I) and other mimetic peptides that form a belt around HDL. Here, we report the crystal structure of LCAT with an extended lid that blocks access to the active site, consistent with an inactive conformation. Residues Thr-123 and Phe-382 in the catalytic domain form a latch-like interaction with hydrophobic residues in the lid. Because these residues are mutated in genetic disease, lid displacement was hypothesized to be an important feature of apoA-I activation. Functional studies of site-directed mutants revealed that loss of latch interactions or the entire lid enhanced activity against soluble ester substrates, and hydrogen-deuterium exchange (HDX) mass spectrometry revealed that the LCAT lid is extremely dynamic in solution. Upon addition of a covalent inhibitor that mimics one of the reaction intermediates, there is an overall decrease in HDX in the lid and adjacent regions of the protein, consistent with ordering. These data suggest a model wherein the active site of LCAT is shielded from soluble substrates by a dynamic lid until it interacts with HDL to allow transesterification to proceed.
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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.