Peptide Models of Lipid-protein Interaction and Protein Aggregation into Amyloids

	Short peptides corresponding to the discrete protein modules offer an attractive system to study the structural and functional details of proteins and several biomolecular processes. We have exploited the manipulative versatility and design diversity offered by short peptides to address the phenomena of fatty acid acylation of proteins in context of their membrane association and of self-assembly of proteins into highly ordered amyloids aggregates. Our studies have shown that covalent modification of proteins with long chain fatty acid serves not just as lipid anchor but also as a regulator of the submembrane topology of the peptide chain. Using short peptides derived from the core sequences of amyloidogenic proteins, we have shown peptide concentration-dependent heterogeneity in amyloids aggregates and the existence of off-pathway aggregates. We have also probed the time-resolved tryptophan fluorescence intensity decay and have demonstrated that the immediate microenvironment of the indole moiety greatly influences the heterogeneity of the tryptophan lifetime distribution.