Conformations of human apolipoprotein E(263-286) and E(267-289) in aqueous solutions of sodium dodecyl sulfate by CD and ¹H NMR

Structures of apoE(263-286) and apoE(267-289) have been determined in aqueous solution containing 90-fold molar excess of perdeuteraled sodium dodecyl sulfate by CD and ¹H NMR. Conformations were calculated by distance geometry based on 370 and 276 NOE distance restraints, respectively. RMSD for superimposing the region 265-284 from an ensemble of 41 structures for apoE- (263-286) is 0.64 ± 0.17 Å for backbone atoms (N, C(α), C=O) and 1.51 ± 0.13 Å for all atoms. The backbone RMSD for an ensemble of 37 structures for apoE(267-289) is 0.74 ± 0.21 Å for the region 268-275 and 0.34 ± 0.10 Å for the region 276-286. A two-domain structure was found for apoE-(267-289) with the C-terminal half adopting a very well defined helix and the N- terminal segment 268-275 a less well defined helix, suggesting that the N- terminus may weakly bind to SDS. For apoE(263-286), an amphipathic helix- band-helix structural motif was found with all hydrophobic side chains on the concave face. The existence of a bend around residues Q273 to G278 is consistent with their temperature coefficients of amide protons as well as secondary shifts of α-protons. Comparison of the structures of the two peptides revealed that the enhanced binding of apoE(263-286) to lipid could be attributed to the formation of a hydrophobic cluster consisting of residues W264, F265, L268, and V269. Aromatic side chains are proposed to be especially important in anchoring apolipoprotein fragments to micelles.