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

Structures of apoE(263-286) and apoE(267-289) have been determined in aqueous solution containing 90-old molar excess of perdeuterated sodium dodecyl sulfate by CD and H-1 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) (263-286) is 0.64 +/- 0.17 Angstrom for backbone atoms (N, C-alpha, C=O) and 1.51 +/- 0.13 Angstrom for all atoms. The backbone RMSD for an ensemble of 37 structures for apoE(267-289) is 0.74 +/- 0.21 Angstrom for the region 268-275 and 0.34 +/- 0.10 Angstrom for the region 276-286. A two-domain structure was found far 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-bend-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 alpha-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.