{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["63(5)"],"submitter":["Balasubramaniam D"],"pubmed_abstract":["Triglycerides (TG) are required for fatty acid transport and storage and are essential for human health. Angiopoietin-like-protein 8 (ANGPTL8) has previously been shown to form a complex with ANGPTL3 that increases circulating TG by potently inhibiting LPL. We also recently showed that the TG-lowering apolipoprotein A5 (ApoA5) decreases TG levels by suppressing ANGPTL3/8-mediated LPL inhibition. To understand how LPL binds ANGPTL3/8 and ApoA5 blocks this interaction, we used hydrogen-deuterium exchange mass-spectrometry and molecular modeling to map binding sites of LPL and ApoA5 on ANGPTL3/8. Remarkably, we found that LPL and ApoA5 both bound a unique ANGPTL3/8 epitope consisting of N-terminal regions of ANGPTL3 and ANGPTL8 that are unmasked upon formation of the ANGPTL3/8 complex. We fur"],"journal":["Journal of lipid research"],"pagination":["100198"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9036128"],"repository":["biostudies-literature"],"pubmed_title":["An anti-ANGPTL3/8 antibody decreases circulating triglycerides by binding to a LPL-inhibitory leucine zipper-like motif."],"pmcid":["PMC9036128"],"pubmed_authors":["Fitchett JR","Siegel RW","Konrad RJ","Day JW","Heng AR","Schroeder O","Jones BE","Chen YQ","Austin AK","Balasubramaniam D","Qian YW","Russell AM","Zhen EY","Davies J","Glaesner W","Beyer TP","Ehsani M"],"additional_accession":[]},"is_claimable":false,"name":"An anti-ANGPTL3/8 antibody decreases circulating triglycerides by binding to a LPL-inhibitory leucine zipper-like motif.","description":"Triglycerides (TG) are required for fatty acid transport and storage and are essential for human health. Angiopoietin-like-protein 8 (ANGPTL8) has previously been shown to form a complex with ANGPTL3 that increases circulating TG by potently inhibiting LPL. We also recently showed that the TG-lowering apolipoprotein A5 (ApoA5) decreases TG levels by suppressing ANGPTL3/8-mediated LPL inhibition. To understand how LPL binds ANGPTL3/8 and ApoA5 blocks this interaction, we used hydrogen-deuterium exchange mass-spectrometry and molecular modeling to map binding sites of LPL and ApoA5 on ANGPTL3/8. Remarkably, we found that LPL and ApoA5 both bound a unique ANGPTL3/8 epitope consisting of N-terminal regions of ANGPTL3 and ANGPTL8 that are unmasked upon formation of the ANGPTL3/8 complex. We fur","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-04-26T15:23:35.144Z","creation":"2025-04-06T14:52:32.333Z"},"accession":"S-EPMC9036128","cross_references":{"pubmed":["35307397"],"doi":["10.1016/j.jlr.2022.100198"]}}