ArticleProceedings of the National Academy of Sciences of the United States of America2021
The intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. 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, 46 citations in OpenAlex.
- GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Recent Advancements in Understanding the Role and Mechanisms of Angiopoietin-like Proteins in Diabetic Retinopathy.Metabolites · 2025Review
- 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
- Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1.Journal of lipid research · 2025Article
- Review
- Adipose Factor ANGPTL4: Its Role in Aging Mechanisms and Associated Diseases.Clinical interventions in aging · 2025Review
- A negatively charged cluster in the disordered acidic domain of GPIHBP1 provides selectivity in the interaction with lipoprotein lipase.Scientific reports · 2024Article
- APOA5 deficiency causes hypertriglyceridemia by reducing amounts of lipoprotein lipase in capillaries.Journal of lipid research · 2024Review
- Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Endothelial lipase variant T111I does not alter inhibition by angiopoietin-like proteins.Scientific reports · 2024Article
- Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen.The Journal of clinical investigation · 2023Article
- Conformationally Restricted Glycopeptide Backbone Inhibits Gas-Phase H/D Scrambling between Glycan and Peptide Moieties.Journal of the American Chemical Society · 2023Article
- The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The association between biomarker angiopoietin-like protein five and obstructive sleep apnea in patients undergoing bariatric surgery.Sleep & breathing = Schlaf & Atmung · 2023Article
- Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Link between Magnesium Supplements and Statin Medication in Dyslipidemic Patients.Current issues in molecular biology · 2023Review
- Intracapillary LPL levels in brown adipose tissue, visualized with an antibody-based approach, are regulated by ANGPTL4 at thermoneutral temperatures.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Angiopoietin-like protein 4/8 complex-mediated plasmin generation leads to cleavage of the complex and restoration of LPL activity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A protein of capillary endothelial cells, GPIHBP1, is crucial for plasma triglyceride metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells.The Journal of clinical investigation · 2022Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The complex between lipoprotein lipase (LPL) and its endothelial receptor (GPIHBP1) is responsible for the lipolytic processing of triglyceride-rich lipoproteins (TRLs) along the capillary lumen, a physiologic process that releases lipid nutrients for vital organs such as heart and skeletal muscle. LPL activity is regulated in a tissue-specific manner by endogenous inhibitors (angiopoietin-like [ANGPTL] proteins 3, 4, and 8), but the molecular mechanisms are incompletely understood. ANGPTL4 catalyzes the inactivation of LPL monomers by triggering the irreversible unfolding of LPL's α/β-hydrolase domain. Here, we show that this unfolding is initiated by the binding of ANGPTL4 to sequences near LPL's catalytic site, including β2, β3-α3, and the lid. Using pulse-labeling hydrogen‒deuterium exchange mass spectrometry, we found that ANGPTL4 binding initiates conformational changes that are nucleated on β3-α3 and progress to β5 and β4-α4, ultimately leading to the irreversible unfolding of regions that form LPL's catalytic pocket. LPL unfolding is context dependent and varies with the thermal stability of LPL's α/β-hydrolase domain (
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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.