ArticleThe Journal of biological chemistry2019
Mapping the sites of the lipoprotein lipase (LPL)-angiopoietin-like protein 4 (ANGPTL4) interaction provides mechanistic insight into LPL inhibition.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Factors Influencing Anxiety and Depression Symptoms in Patients With Acute Ischaemic Stroke and the Development and Validation of a Risk Prediction Model.Actas espanolas de psiquiatria · 2026Article
- Sustained-release CGRP microspheres accelerate diabetic wound healing by synergistically promoting neurovascular regeneration through modulation of macrophage and endothelial cell functions.Materials today. Bio · 2026Article
- Evaluating the Cardiometabolic Efficacy and Safety of Lipoprotein Lipase Pathway Targets in Combination With Approved Lipid-Lowering Targets: A Drug Target Mendelian Randomization Study.Circulation. Genomic and precision medicine · 2025Article
- ANGPTL3/8 is an atypical unfoldase that regulates intravascular lipolysis by catalyzing unfolding of lipoprotein lipase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comprehensive profiling of chemokine and NETosis-associated genes in sarcopenia: construction of a machine learning-based diagnostic nomogram.Frontiers in medicine · 2025Article
- Exercise-Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism.Health science reports · 2024Review
- Examining DNA Structures with In-droplet Hydrogen/Deuterium Exchange Mass Spectrometry.International journal of mass spectrometry · 2024Article
- ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.Journal of translational medicine · 2024Article
- Macromolecular Interactions of Lipoprotein Lipase (LPL).Sub-cellular biochemistry · 2024Review
- Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis.Nature communications · 2023Article
- Combined action of albumin and heparin regulates lipoprotein lipase oligomerization, stability, and ligand interactions.PloS one · 2023Article
- ANGPTL4, IL-6 and TNF-α as regulators of lipid metabolism during a marathon run.Scientific reports · 2022Article
- Lipoprotein size is a main determinant for the rate of hydrolysis by exogenous LPL in human plasma.Journal of lipid research · 2022Article
- Using Synthetic ApoC-II Peptides and nAngptl4 Fragments to Measure Lipoprotein Lipase Activity in Radiometric and Fluorescent Assays.Frontiers in cardiovascular medicine · 2022Article
- Article
- Hepatocyte-specific suppression of ANGPTL4 improves obesity-associated diabetes and mitigates atherosclerosis in mice.The Journal of clinical investigation · 2021Article
- The intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity.Frontiers in cell and developmental biology · 2021Review
- Lipoprotein Lipase and Its Regulators: An Unfolding Story.Trends in endocrinology and metabolism: TEM · 2021Review
- Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids.Journal of lipid research · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiovascular disease has been the leading cause of death throughout the world for nearly 2 decades. Hypertriglyceridemia affects more than one-third of the population in the United States and is an independent risk factor for cardiovascular disease. Despite the frequency of hypertriglyceridemia, treatment options are primarily limited to diet and exercise. Lipoprotein lipase (LPL) is an enzyme responsible for clearing triglycerides from circulation, and its activity alone can directly control plasma triglyceride concentrations. Therefore, LPL is a good target for triglyceride-lowering therapeutics. One approach for treating hypertriglyceridemia may be to increase the amount of enzymatically active LPL by preventing its inhibition by angiopoietin-like protein 4 (ANGPTL4). However, little is known about how these two proteins interact. Therefore, we used hydrogen-deuterium exchange MS to identify potential binding sites between LPL and ANGPTL4. We validated sites predicted to be located at the protein-protein interface by using chimeric variants of LPL and an LPL peptide mimetic. We found that ANGPTL4 binds LPL near the active site at the lid domain and a nearby α-helix. Lipase lid domains cover the active site to control both enzyme activation and substrate specificity. Our findings suggest that ANGPTL4 specifically inhibits LPL by binding the lid domain, which could prevent substrate catalysis at the active site. The structural details of the LPL-ANGPTL4 interaction uncovered here may inform the development of therapeutics targeted to disrupt this interaction for the management of hypertriglyceridemia.
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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.