title: Lysine residues of ABCA1 are required for the interaction with apoA-I.
abstract: ATP-binding cassette protein A1 (ABCA1) plays a pivotal role in cholesterol homeostasis by generating high-density lipoprotein (HDL). Apolipoprotein A-I (apoA-I), a lipid acceptor for ABCA1, reportedly interacts with ABCA1. However, it has also been proposed that apoA-I interacts with ABCA1-generated special domains on the plasma membrane, but apart from ABCA1, and solubilizes membrane lipids. To determine the importance of the apoA-I-ABCA1 interaction in HDL formation, the electrostatic interaction between apoA-I and ABCA1, which mediates the interaction between apoB100 in low-density lipoprotein particles (LDL) and LDL receptor, was analyzed. The apoA-I binding to ABCA1 and the cross-linking between them were inhibited by the highly charged molecules heparin and poly-L-lysine. Treating cells with membrane impermeable reagents that specifically react with primary amino groups abolished the interaction between apoA-I and ABCA1. However, these reagents did not affect the characteristic tight ATP binding to ABCA1. These results suggest that lysine residues in the extracellular domains of ABCA1 contribute to the interaction with apoA-I. The electrostatic interaction between ABCA1 and apoA-I is predicted to be the first step in HDL formation. This article is part of a Special Issue entitled Advances in high density lipoprotein formation and metabolism: a tribute to John F. Oram (1945-2010).
authors.affiliation: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Nagao
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D001710:Biotin / Q000031:analogs & derivatives / Q000737:chemistry; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013388:Succinimides / Q000737:chemistry
chemical_list: C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D013388:Succinimides; C033788:biotinyl N-hydroxysuccinimide ester; D001710:Biotin; D000255:Adenosine Triphosphate; D002784:Cholesterol; D008239:Lysine