Contributions of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins.
Exchangeable apolipoproteins function in lipid transport as structural components of lipoprotein particles, cofactors for enzymes and ligands for cell-surface receptors. Recent findings with apoA-I and apoE suggest that the tertiary structures of these two members of the human exchangeable apolipoprotein gene family are related. Characteristically, these proteins contain a series of proline-punctuated, 11- or 22-amino acid, amphipathic alpha-helical repeats that can adopt a helix bundle conformation in the lipid-free state. The amino- and carboxyl-terminal regions form separate domains with the latter being primarily responsible for lipid binding. Interaction with lipid induces changes in the conformation of the amino-terminal domain leading to alterations in function; for example, opening of the amino-terminal four-helix bundle in apolipoprotein E upon lipid binding is associated with enhanced receptor-binding activity. The concept of a two-domain structure for the larger exchangeable apolipoproteins is providing new molecular insights into how these apolipoproteins interact with lipids and other proteins, such as receptors. The ways in which structural changes induced by lipid interaction modulate the functionality of these apolipoproteins are reviewed.
Saito
Hiroyuki
H
Lipid Research Group, The Children's Hospital of Philadelphia, Abramson Research Center, Suite 1102, 3615 Civic Center Boulevard, University of Pennsylvania School of Medicine, Philadelphia, 19104-4318, USA.
Lund-Katz
Sissel
S
Phillips
Michael C
MC
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism; D001053:Apolipoproteins / Q000378:metabolism*; D001054:Apolipoproteins A / Q000378:metabolism; D001056:Apolipoproteins C / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008956:Models, Chemical; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D001057:Apolipoproteins E