title: Structure-function relationships of apolipoprotein A-I: a flexible protein with dynamic lipid associations.
abstract: OBJECTIVE
  Apolipoprotein A-I is the major structural protein of HDL. Its physicochemical properties maintain a delicate balance between maintenance of stable lipoproteins and the ability to associate with and dissociate from the lipid transported. Here we review the progress made in the last 2-3 years on the structure-function relationships of apolipoprotein A-I, including elements related to the ATP binding cassette transporter A1.
  
  
  RESULTS
  Current evidence now supports the so-called 'belt' or 'hairpin' models for apolipoprotein A-I conformation when bound to discoidal lipoproteins. In-vivo expression of apolipoprotein A-I mutant proteins has shown that both the N- and C-terminal domains are important for lipid association as well as for the esterification reaction, particularly binding of cholesteryl esters and formation of mature alpha-migrating lipoproteins. This property is apparently quite distinct from the activation of the enzyme lecithin cholesterol acyl transferase, which requires interaction with the central helix 6. The interaction of apolipoprotein A-I with the ATP binding cassette transporter A1 has been shown to require the C-terminal domain, which is proposed to mediate the opening of the helix bundle formed by lipid-free or lipid-poor apolipoprotein A-I and allow its association with hydrophobic binding sites.
  
  
  CONCLUSIONS
  Significant progress has been made in the understanding of the molecular mechanisms controlling the folding of apolipoprotein A-I and its interaction with lipids and various other protein factors involved in HDL metabolism.
authors.affiliation: Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, Room H460, 40 Ruskin Street, Ottawa, Ontario, Canada, K1Y 4W7. ymarcel@ottawaheart.ca
authors.forename: Yves L
authors.initials: YL
authors.lastname: Marcel
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kiss
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D016632:Apolipoprotein A-I