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 perdeuterated 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 A for backbone atoms (N, C alpha, C = O) and 1.51 +/- 0.13 A for all atoms. The backbone RMSD for an ensemble of 37 structures for apoE(267-289) is 0.74 +/- 0.21 A for the region 268-275 and 0.34 +/- 0.10 A 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-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.