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An orphan dermaseptin from frog skin reversibly assembles to amyloid‐like aggregates in a pH‐dependent fashion
Author(s) -
GößlerSchöfberger Ruth,
Hesser Günter,
Muik Martin,
Wechselberger Christian,
Jilek Alexander
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07266.x
Subject(s) - chemistry , frog skin , peptide , amphiphile , biophysics , amyloid (mycology) , antimicrobial peptides , helix (gastropod) , side chain , folding (dsp implementation) , aqueous solution , crystallography , stereochemistry , biochemistry , organic chemistry , polymer , snail , biology , engineering , inorganic chemistry , ecology , electrical engineering , copolymer , sodium
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 α 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 5–6.5), however, ‘backward’ granular aggregates, 10–500 nm in size, are formed. Such metastable amorphous aggregates, which are quickly released from an amyloid depot by a shift in pH, can mediate a strong cytotoxic effect. This activity does not involve lysis or interference with the cellular redox status, but apparently acts via an as yet unidentified mechanism. In this study, we present a new member of an emerging class of self‐assembling frog skin peptides with extraordinary self‐aggregation properties, which may potentially be relevant for biological processes. Structured digital abstract• MINT‐7256467 : Dermaseptin (uniprotkb: O93455 ) and Dermaseptin (uniprotkb: O93455 ) bind ( MI:0407 ) by circular dichroism ( MI:0016 ) • MINT‐7255686 : Dermaseptin (uniprotkb: O93455 ) and Dermaseptin (uniprotkb: O93455 ) bind ( MI:0407 ) by biophysical ( MI:0013 ) • MINT‐7256439 : Dermaseptin (uniprotkb: O93455 ) and Dermaseptin (uniprotkb: O93455 ) bind ( MI:0407 ) by fluorescence microscopy ( MI:0416 ) • MINT‐7256449 : Dermaseptin (uniprotkb: O93455 ) and Dermaseptin (uniprotkb: O93455 ) bind ( MI:0407 ) by electron microscopy ( MI:0040 ) • MINT‐7256430 : Dermaseptin (uniprotkb: O93455 ) and Dermaseptin (uniprotkb: O93455 ) bind ( MI:0407 ) by fluorescence technologies ( MI:0051 )