title: Difference in lipid packing sensitivity of exchangeable apolipoproteins apoA-I and apoA-II: an important determinant for their distinctive role in lipid metabolism.
abstract: Exchangeable apolipoproteins A-I and A-II play distinct roles in reverse cholesterol transport. ApoA-I interacts with phospholipids and cholesterol of the cell membrane to make high density lipoprotein particles whereas apolipoprotein A-II interacts with high density lipoprotein particles to release apolipoprotein A-I. The two proteins show a high activity at the aqueous solution/lipid interface and are characterized by a high content of amphipathic α-helices built upon repetition of the same structural motif. We set out to investigate to what extent the number of α-helix repeats of this structural motif modulates the affinity of the protein for lipids and the sensitivity to lipid packing. To this aim we have compared the insertion of apolipoproteins A-I and A-II in phospholipid monolayers formed on a Langmuir trough in conditions where lipid packing, surface pressure and charge were controlled. We also used atomic force microscopy to obtain high resolution topographic images of the surface at a resolution of several nanometers and performed statistical image analysis to calculate the spatial distribution and geometrical shape of apolipoproteins A-I and A-II clusters. Our data indicate that apolipoprotein A-I is sensitive to packing of zwitterionic lipids but insensitive to the packing of negatively charged lipids. Interestingly, apolipoprotein A-II proved to be insensitive to the packing of zwitterionic lipids. The different sensitivity to lipid packing provides clues as to why apolipoprotein A-II barely forms nascent high density lipoprotein particles while apolipoprotein A-I promotes their formation. We conclude that the different interfacial behaviors of apolipoprotein A-I and apolipoprotein A-II in lipidic monolayers are important determinants of their distinctive roles in lipid metabolism.
authors.affiliation: Institut de Physique de Rennes, UMR-CNRS 6251 Université de Rennes 1, Campus de Beaulieu, Rennes cedex, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Chièze
authors.forename: Victor Martin
authors.initials: VM
authors.lastname: Bolanos-Garcia
authors.forename: Gérard
authors.initials: G
authors.lastname: Le Caër
authors.forename: Anne
authors.initials: A
authors.lastname: Renault
authors.forename: Véronique
authors.initials: V
authors.lastname: Vié
authors.forename: Sylvie
authors.initials: S
authors.lastname: Beaufils
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D018625:Microscopy, Atomic Force; D010743:Phospholipids / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D010743:Phospholipids; D011994:Recombinant Proteins