Specific sequences in the N and C termini of apolipoprotein A-IV modulate its conformation and lipid association |
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Authors: | Pearson Kevin Tubb Matthew R Tanaka Masafumi Zhang Xiu Qi Tso Patrick Weinberg Richard B Davidson W Sean |
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Institution: | Department of Pathology and Laboratory Medicine, The University of Cincinnati, Cincinnati, Ohio 45237-0507, USA. |
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Abstract: | Apolipoprotein (apoA-IV) is a 376-residue exchangeable apolipoprotein that may play a number of important roles in lipid metabolism, including chylomicron assembly, reverse cholesterol transport, and appetite regulation. In vivo, apoA-IV exists in both lipid-poor and lipid-associated forms, and the balance between these states may determine its function. We examined the structural elements that modulate apoA-IV lipid binding by producing a series of deletion mutants and determining their ability to interact with phospholipid liposomes. We found that the deletion of residues 333-343 strongly increased the lipid association rate versus native apoA-IV. Additional mutagenesis revealed that two phenylalanine residues at positions 334 and 335 mediated this lipid binding inhibitory effect. We also observed that residues 11-20 in the N terminus were required for the enhanced lipid affinity induced by deletion of the C-terminal sequence. We propose a structural model in which these sequences can modulate the conformation and lipid affinity of apoA-IV. |
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