tailieunhanh - Báo cáo khoa học: An orphan dermaseptin from frog skin reversibly assembles to amyloid-like aggregates in a pH-dependent fashion

Dermaseptin PD-3-7 (aDrs) from frog skin contains three aspartic acid resi-dues resulting in a negative net charge at neutral pH, as opposed to numer-ous other dermaseptins which are cationic helical antimicrobial peptides. Still, this peptide can be fitted into an amphipathicahelix by an Edmundson wheel projection. | ỊFEBS Journal An orphan dermaseptin from frog skin reversibly assembles to amyloid-like aggregates in a pH-dependent fashion Ruth GoBler-Schofberger1 Gunter Hesser2 Martin Muik3 Christian Wechselberger4 and Alexander Jilek1 1 Institute of Organic Chemistry Johannes Kepler University Linz Austria 2 CSNA Center for Surface- and Nanoanalytics Johannes Kepler University Linz Austria 3 Institute of Biophysics Johannes Kepler University Linz Austria 4 Center for BiomedicalNanotechnology Upper Austrian Research Linz Austria Keywords amphibian skin amyloid bioactive peptide cytotoxicity self-assembly Correspondence A. Jilek Institute of Organic Chemistry Johannes Kepler University Linz Altenbergerstrasse 69 A-4040 Linz Austria Fax 43 732 2468 8747 Tel 43 732 2468 9498 E-mail Received 6 April2008 revised 5 August 2009 accepted 7 August 2009 doi Dermaseptin PD-3-7 aDrs from frog skin contains three aspartic acid residues resulting in a negative net charge at neutral pH as opposed to numerous other dermaseptins which are cationic helical antimicrobial peptides. Still this peptide can be fitted into an amphipathic a helix by an Edmundson wheel projection. However folding to the proposed helix was induced to only a low extent by zwitterionic vesicles or even detergents. Furthermore no evidence of antibacterial or cytotoxic activity from soluble aDrs could be obtained. The peptide has an inherent propensity to an extended conformation in aqueous solution and self-assembles into amyloid fibrils in a reversible pH-controlled fashion which was studied in some detail above pH 5 the amyloid fibrils disassemble in a cooperative manner. This is probably caused by deprotonation of both side chain and terminal carboxyl groups which results in intermolecular electrostatic repulsion. At neutral pH this process proceeds instantaneously to the soluble form. Within the transition interval pH however backward granular aggregates 10-500 .