Abstract
The mechanism of membrane interaction by β‐sheet peptides is important to understand fundamental principles of folding of β‐barrel proteins and various β‐amyloid proteins. Here, we examined the conformational characteristics of a porin‐like channel forming (__x__S__x__G)~6~ peptide in solution and membrane‐mimicking environments (CD and ATR–IR) to understand the structural changes of the peptide during membrane association and channel formation. A comparison of the peptide conformations in different microenvironments showed that β‐sheet formation is enhanced in membrane‐mimicking liposomes and SDS‐micelles. The lipid‐induced β‐sheet formation was confirmed by the formation of a characteristic β‐sheet structure on mixing a methanolic solution of the peptide (partially folded) with preformed liposomes. The amphipathicity of the peptide; increased hydrogen bonding, hydrophilicity, and reduction in dimensionality of the membrane surface; membrane–peptide interaction–forces; and presence of flexible glycines might facilitate β‐sheet formation in membranes. Though the CD spectra of both the peptide‐bound and peptide‐incorporated lipids are reminiscent of a β‐sheet structure, a significant variation in the peak positions of the two β‐sheet structures was noticed. The channel characteristics of (__x__S__x__G)~6~ in the presence of low ionic strength solutions of NEt~3~BzCl and glucosammonium chloride are comparable to those reported under high ionic strength solutions. Altogether the data suggest that the channel formation by (__x__S__x__G)~6~ proceeds via β‐sheet aggregate formation at the membrane surface, β‐sheet insertion, and rearrangement into a β‐barrel–like structure. The β‐barrel–like channel formation most likely arises from a sequence similarity to β‐barrel porins whereas the lipid‐induced β‐sheet formation is governed by the above‐mentioned factors. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 317–328, 2006
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