1l6l
From Proteopedia
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Structures of Apolipoprotein A-II and a Lipid Surrogate Complex Provide Insights into Apolipoprotein-Lipid Interactions
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Overview
Apolipoproteins A-I and A-II form the major protein constituents of, high-density lipid particles (HDL), the concentration of which is, inversely correlated with the frequency of heart disease in humans., Although the physiological role of apolipoprotein A-II is unclear, evidence for its involvement in free fatty acid metabolism in mice has, recently been obtained. Currently, the best characterized activity of, apolipoprotein A-II is its potent antagonism of the anti-atherogenic and, anti-inflammatory activities of apolipoprotein A-I, probably due to its, competition with the latter for lipid acyl side chains in HDL. Many, interactions of apolipoprotein A-I with enzymes and proteins involved in, reverse cholesterol transport and HDL maturation are mediated by, lipid-bound protein. The structural bases of interaction with lipids are, expected to be common to exchangeable apolipoproteins and attributable to, amphipathic alpha-helices present in each of them. Thus, characterization, of apolipoprotein-lipid interactions in any apolipoprotein is likely to, provide information that is applicable to the entire class. We report, structures of human apolipoprotein A-II and its complex with beta-octyl, glucoside, a widely used lipid surrogate. The former shows that, disulfide-linked dimers of apolipoprotein A-II form amphipathic, alpha-helices which aggregate into tetramers. Dramatic changes, observed, in the presence of beta-octyl glucoside, might provide clues to the, structural basis for its antagonism of apolipoprotein A-I. Additionally, excursions of individual molecules of apolipoprotein A-II from a common, helical architecture in both structures indicate that lipid-bound, apolipoproteins are likely to have an ensemble of related conformations., These structures provide the first experimental paradigm for description, of apolipoprotein-lipid interactions at the atomic level.
Disease
Known diseases associated with this structure: Apolipoprotein A-II deficiency OMIM:[107670], Hypercholesterolemia, familial, modification of OMIM:[107670]
About this Structure
1L6L is a Single protein structure of sequence from Homo sapiens with BOG as ligand. Full crystallographic information is available from OCA.
Reference
Structures of apolipoprotein A-II and a lipid-surrogate complex provide insights into apolipoprotein-lipid interactions., Kumar MS, Carson M, Hussain MM, Murthy HM, Biochemistry. 2002 Oct 1;41(39):11681-91. PMID:12269810
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