title: Apolipoprotein A-II-mediated conformational changes of apolipoprotein A-I in discoidal high density lipoproteins.
abstract: It is well accepted that HDL has the ability to reduce risks for several chronic diseases. To gain insights into the functional properties of HDL, it is critical to understand the HDL structure in detail. To understand interactions between the two major apolipoproteins (apos), apoA-I and apoA-II in HDL, we generated highly defined benchmark discoidal HDL particles. These particles were reconstituted using a physiologically relevant phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) incorporating two molecules of apoA-I and one homodimer of apoA-II per particle. We utilized two independent mass spectrometry techniques to study these particles. The techniques are both sensitive to protein conformation and interactions and are namely: 1) hydrogen deuterium exchange combined with mass spectrometry and 2) partial acetylation of lysine residues combined with MS. Comparison of mixed particles with apoA-I only particles of similar diameter revealed that the changes in apoA-I conformation in the presence of apoA-II are confined to apoA-I helices 3-4 and 7-9. We discuss these findings with respect to the relative reactivity of these two particle types toward a major plasma enzyme, lecithin:cholesterol acyltransferase responsible for the HDL maturation process.
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Lipids and Atherosclerosis Sciences, University of Cincinnati, Cincinnati, Ohio 45267, USA.
authors.forename: Kekulawalage
authors.initials: K
authors.lastname: Gauthamadasa
authors.forename: Nataraja Sarma
authors.initials: NS
authors.lastname: Vaitinadin
authors.forename: James L
authors.initials: JL
authors.lastname: Dressman
authors.forename: Stephen
authors.initials: S
authors.lastname: Macha
authors.forename: Reyn
authors.initials: R
authors.lastname: Homan
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Greis
authors.forename: R A Gangani D
authors.initials: RA
authors.lastname: Silva
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000737:chemistry* / Q000378:metabolism; D041961:Deuterium Exchange Measurement; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; C034366:discoidal lipoproteins; C028694:1-palmitoyl-2-oleoylphosphatidylcholine