Oct 24, 2018

Staphylococcus aureus PSMα3 Cross-α Fibril Polymorphism and Determinants of Cytotoxicity

BioRxiv : the Preprint Server for Biology
Einav Tayeb-FligelmanMeytal Landau

Abstract

The phenol-soluble modulin (PSM) peptide family, secreted by Staphylococcus aureus , performs various virulence activities, some mediated by the formation of amyloid fibrils of diverse architectures. Specifically, PSMα1 and PSMα4 structure the S. aureus biofilm by assembling into robust cross-β amyloid fibrils. PSMα3, the most cytotoxic member of the family, assembles into cross-α fibrils in which α-helices stack into tightly mated sheets, mimicking the cross-β architecture. Here we demonstrated that massive T-cell deformation and death is linked with PSMα3 aggregation and co-localization with cell membranes. Our extensive mutagenesis analyses supported the role of positive charges, and especially Lys17, in interactions with the membrane, and suggested their regulation by inter- and intra-helical electrostatic interactions within the cross-α fibril. We hypothesize that PSMα3 cytotoxicity is governed by the ability to form cross-α fibrils and involves a dynamic process of co-aggregation with cell membrane, rupturing it.

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Mentioned in this Paper

Phenol
Derivatives
APP protein, human
Aggregation
Fibrillation
Helice
Mutant Proteins
Soluble
Toxic Effect
Amyloid Deposition

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