Involvement of electrostatic interactions in the mechanism of peptide folding induced by sodium dodecyl sulfate binding

Sodium dodecyl sulfate (SDS) has consistently been shown to induce secondar y structure, particularly or-helices, in polypeptides, and is commonly used to model membrane and other hydrophobic environments. However, the precise mechanism by which SDS induces these conformational changes remains unclea r. To examine the role of electrostatic interactions in this mechanism, we have designed two hydrophilic, charged amphipathic alpha-helical peptides, one basic (QAPAYKKAAKKLAES) and the other acidic (QAPAYEEAAEELAKS), and the ir structures were studied by CD and NMR. The design of the peptides is bas ed on the sequence of the segment of residues 56-70 of human platelet facto r 4 [PF4-(56-70), QAPLYKKIIKKLLES]. Both peptides were unstructured in wate r, and in the presence of neutral, zwitterionic, or cationic detergents. Ho wever, in SDS at neutral pH, the basic peptide folded into an alpha-helix. By contrast, the pH needed to be lowered to 1.8 before alpha-helix formatio n was observed for the acidic peptide. Strong, attractive electrostatic int eractions, between the anionic groups of SDS and the cationic groups of the lysines, appeared to be necessary to initiate the folding of the basic pep tide. NMR analysis showed that the basic peptide was fully embedded in SDS- peptide micelles, and that its three-dimensional. alpha-helical structure c ould be superimposed on that of the native structure of PF4(56-70). These r esults enabled us to propose a working model of the basic peptide-SDS compl ex, and a mechanism for SDS-induced alpha-helical folding. This study demon strates that, while the folding of peptides is mostly driven by hydrophobic effects, electrostatic interactions play a significant role in the formati on and the stabilization of SDS-induced structure.