ABCA1 and amphipathic apolipoproteins form high-affinity molecular complexes required for cholesterol efflux
Open Access
- 1 February 2004
- journal article
- Published by Elsevier BV in Journal of Lipid Research
- Vol. 45 (2), 287-294
- https://doi.org/10.1194/jlr.m300355-jlr200
Abstract
Apolipoproteins, such as apolipoprotein A-I (apoA-I), can stimulate cholesterol efflux from cells expressing the ATP binding cassette transporter A1 (ABCA1). The nature of the molecular interaction between these cholesterol acceptors and ABCA1 is controversial, and models suggesting a direct protein-protein interaction or indirect association have been proposed. To explore this issue, we performed competition binding and chemical cross-linking assays using six amphipathic plasma proteins and an 18 amino acid amphipathic helical peptide. All seven proteins stimulated lipid efflux and inhibited the cross-linking of apoA-I to ABCA1. Cross-linking of apoA-I to ABCA1 was saturable and occurred at high affinity (Kd of 7.0 ± 1.9 nM), as was cross-linking of apoA-II. After binding to ABCA1, apoA-I rapidly dissociated (half-life of 25 min) from the complex and was released back into the medium. A mutant form of ABCA1 (W590S) that avidly binds apoA-I but fails to promote cholesterol efflux released apoA-I with similar kinetics but without transfer of cholesterol to apoA-I.Keywords
This publication has 18 references indexed in Scilit:
- Regulation and Mechanisms of ATP-Binding Cassette Transporter A1-Mediated Cellular Cholesterol EffluxArteriosclerosis, Thrombosis, and Vascular Biology, 2003
- ABCA1 redistributes membrane cholesterol independent of apolipoprotein interactionsJournal of Lipid Research, 2003
- A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-IJCI Insight, 2003
- Distinct sites on ABCA1 control distinct steps required for cellular release of phospholipidsJournal of Lipid Research, 2002
- The Role of Apolipoprotein A-I Helix 10 in Apolipoprotein-mediated Cholesterol Efflux via the ATP-binding Cassette Transporter ABCA1Published by Elsevier BV ,2002
- Naturally Occurring Mutations in the Largest Extracellular Loops of ABCA1 Can Disrupt Its Direct Interaction with Apolipoprotein A-IPublished by Elsevier BV ,2002
- Specific Docking of Apolipoprotein A-I at the Cell Surface Requires a Functional ABCA1 TransporterPublished by Elsevier BV ,2001
- ABCA1 Is the cAMP-inducible Apolipoprotein Receptor That Mediates Cholesterol Secretion from MacrophagesPublished by Elsevier BV ,2000
- Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1Journal of Biological Chemistry, 2000
- Apolipoprotein-mediated Plasma Membrane MicrosolubilizationJournal of Biological Chemistry, 1999