title: Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces.
abstract: Apolipoprotein A-I (apoA-I) has a great conformational flexibility to exist in lipid-free, lipid-poor, and lipid-bound states during lipid metabolism. To address the lipid binding and the dynamic desorption behavior of apoA-I at lipoprotein surfaces, apoA-I, Δ(185-243)apoA-I, and Δ(1-59)(185-243)apoA-I were studied at triolein/water and phosphatidylcholine/triolein/water interfaces with special attention to surface pressure. All three proteins are surface active to both interfaces lowering the interfacial tension and thus increasing the surface pressure to modify the interfaces. Δ(185-243)apoA-I adsorbs much more slowly and lowers the interfacial tension less than full-length apoA-I, confirming that the C-terminal domain (residues 185-243) initiates the lipid binding. Δ(1-59)(185-243)apoA-I binds more rapidly and lowers the interfacial tension more than Δ(185-243)apoA-I, suggesting that destabilizing the N-terminal α-helical bundle (residues 1-185) restores lipid binding. The three proteins desorb from both interfaces at different surface pressures revealing that different domains of apoA-I possess different lipid affinity. Δ(1-59)(185-243)apoA-I desorbs at lower pressures compared with apoA-I and Δ(185-243)apoA-I indicating that it is missing a strong lipid association motif. We propose that during lipoprotein remodeling, surface pressure mediates the adsorption and partial or full desorption of apoA-I allowing it to exchange among different lipoproteins and adopt various conformations to facilitate its multiple functions.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118.
authors.forename: Libo
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Mei
authors.forename: David
authors.initials: D
authors.lastname: Atkinson
authors.forename: Donald M
authors.initials: DM
authors.lastname: Small
mesh_terms: D000327:Adsorption; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism; D009154:Mutation; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013499:Surface Properties; D013816:Thermodynamics; D014304:Triolein / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D008074:Lipoproteins; D010713:Phosphatidylcholines; D014867:Water; D014304:Triolein
keywords: adsorption and desorption; conformational flexibility; interfacial tension; lipid affinity; lipid association motif; lipid binding; phosphatidylcholine/triolein/water interface; surface pressure; triolein/water interface