6GQ2

Crystal Structure of the PSMalpha3 Peptide Mutant K12A Forming Cross-Alpha Amyloid-like Fibril

Summary for 6GQ2

• Entry DOI: 10.2210/pdb6gq2/pdb
• Descriptor: Phenol-soluble modulin alpha 3 peptide, SULFATE ION (3 entities in total)
• Functional Keywords: cross-alpha, fibril, amyloid, mating alpha-helical sheets, protein fibril
• Biological source: Staphylococcus aureus RF122
• Total number of polymer chains: 1
• Total formula weight: 2649.11

Authors

Landau, M.,Tayeb-Fligelman, E. (deposition date: 2018-06-07, release date: 2019-06-19, Last modification date: 2024-05-15)

Primary citation

Tayeb-Fligelman, E.,Salinas, N.,Tabachnikov, O.,Landau, M.
Staphylococcus aureus PSM alpha 3 Cross-alpha Fibril Polymorphism and Determinants of Cytotoxicity.
Structure, 28:301-313.e6, 2020

PubMed 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 demonstrate that massive T cell deformation and death are linked with PSMα3 aggregation and co-localization with cell membranes. Our extensive mutagenesis analyses support the role of positive charges, and especially Lys17, in interactions with the membrane and suggest 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 the cell membrane, rupturing it.

PubMed: 31918959
DOI: 10.1016/j.str.2019.12.006

Experimental method

X-RAY DIFFRACTION (1.54 Å)