Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces

Abstract

This article is available online at http://www.jlr.org properties of apoA-I arise primarily through its important roles in the pathway of reverse cholesterol transport; where apoA-I stabilizes and maintains the structure of HDL particles, promotes cellular cholesterol effl ux by binding to specifi c ATP binding cassette transporters, interacts with the enzyme lecithin:cholesterol acyltransferase (LCAT) to drive the maturation of HDL particles, binds and modifi es the lipoprotein surface to facilitate enzyme reactions, and interacts with the scavenger receptor class B type 1 for selective cholesterol ester (CE) uptake by the liver for excretion ( 2-4 ).ApoA-I exists in lipid-free, lipid-poor, and lipid-bound states in plasma, and exchanges among HDL and TAGrich lipoprotein particles like very low density lipoproteins (VLDLs) and chylomicrons (CMs) ( 5 ). ApoA-I interacts primarily with the hydrocarbon chains of the phospholipids (PL) on discoidal and spherical HDLs ( 6-8 ) and may also interact with the hydrophobic CE core of spherical HDL and the hydrophobic TAG core of TAG-rich lipoproteins. The conformational fl exibility of apoA-I allows it to adopt a variety of conformations involving lipid adsorption, partial or full desorption, and fl exible unfolding and refolding in diverse physical environments to facilitate its multiple functions. Studies of the molecular mechanisms of the lipid association and the conformational fl exibility of apoA-I are essential for understanding the structure-function relationships.ApoA-I has an exon 3 encoded region (residues 1-43), and an exon 4 encoded region (residues 44-243) that contains 10 11/22-mer tandem repeat amino acid segments that are predicted to form class A and class Y amphipathic ␣ -helices (A ␣ Hs) ( 9, 10 ). These A ␣ Hs (helix 1-10) are the lipid binding motif of apoA-I and the structural basis for its multiple functions. Segment deletion and point mutation studies have elucidated the possible conformation and functions for each helical segment (11)(12)(13)(14)(15)(16) Apolipoprotein A-I (apoA-I) is a major protein of high density lipoproteins (HDLs) and is also present on large triacylglycerol (TAG)-rich lipoproteins. Reduced plasma levels of HDL and apoA-I are the key risk factors for atherosclerosis and cardiovascular disease ( 1 ). The anti-atherogenic

A Pressure-dependent Model for the Regulation of Lipoprotein Lipase by Apolipoprotein C-II

“…We can compare these results with those from similar experiments with other exchangeable apolipoproteins and peptides, such as apoC-I (31, 37), apoC-III (Figs. 10 and 11), apoA-I (45,48), and the N-and C-terminal domains of apoA-I (32,42,46). This comparison reveals the ability of apoC-II, relative to these proteins, to bind to and travel with TG-rich lipo- C and D) interfaces.…”

“…Our laboratory has used envelope pressure (⌸ ENV ) to refer to retention pressure (i.e. the highest pressure at which a peptide can be retained on an interface before being ejected) (31,45).…”

A Retained Secretory Signal Peptide Mediates High Density Lipoprotein (HDL) Assembly and Function of Haptoglobin-related Protein

“…Multiple model systems, including triolein emulsions (27), phospholipid monolayers (28), and lipid vesicles (29), have been utilized to gain information about apolipoprotein-lipid interactions. Multiple factors, including acyl chain composition, cholesterol content, protein composition, and surface curvature, may contribute to the degree of lateral van der Waals interactions in HDL.…”

HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity

“…During RCT, apoA-I transitions through multiple lipidation states, during which it assumes an array of conformations ( 47 ). RCT is thus mediated by a spectrum of diverse Only 67 subjects were included in the data adjusted for apoA-I due to insuffi cient sample for nine subjects for apoA-I quantitation and one subject missing cholesterol effl ux data.…”