The interaction of β-amyloid protein fragment (12-28) with lipid environments

Abstract

The neurotoxicity of β-amyloid protein (βAP) fragments may be a result of their solution conformation, which is very sensitive to solution conditions. In this work we describe NMR and CD studies of the conformation of βAP(12-28) in lipid (micelle) environments as a function of pH and lipid type. The interaction of βAP(12-28) with zwitterionic dodecylphosphocholine (DPC) micelles is weak and alters the conformation when compared to water solution alone. By contrast, the interaction of the peptide with anionic sodium dodecylsulfate (SDS) micelles is strong: βAP(12-28) is mostly bound, is α-helical from K16 to V24, and aggregates slowly. The pH-dependent conformational changes of βAP(12-28) in solution occur in the pH range at which the side chain groups of E22, D23, H13, and H14 are deprotonated (pK(a)s ca. 4 and 6.5); the interaction of βAP(12-28) with SDS micelles alters the pH-dependent conformational transitions of the peptide whereas the weak interaction with DPC micelles causes little change.