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TitleStructure of biofilm-forming functional amyloid PSMα1 from .
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 121, Issue 33, Page e2406775121, Year 2024
Publish dateAug 13, 2024
AuthorsKasper Holst Hansen / Chang Hyeock Byeon / Qian Liu / Taner Drace / Thomas Boesen / James F Conway / Maria Andreasen / Ümit Akbey /
PubMed AbstractBiofilm-protected pathogenic causes chronic infections that are difficult to treat. An essential building block of these biofilms are functional amyloid fibrils that assemble from phenol-soluble ...Biofilm-protected pathogenic causes chronic infections that are difficult to treat. An essential building block of these biofilms are functional amyloid fibrils that assemble from phenol-soluble modulins (PSMs). PSMα1 cross-seeds other PSMs into cross-β amyloid folds and is therefore a key element in initiating biofilm formation. However, the paucity of high-resolution structures hinders efforts to prevent amyloid assembly and biofilm formation. Here, we present a 3.5 Å resolution density map of the major PSMα1 fibril form revealing a left-handed cross-β fibril composed of two C-symmetric U-shaped protofilaments whose subunits are unusually tilted out-of-plane. Monomeric α-helical PSMα1 is extremely cytotoxic to cells, despite the moderate toxicity of the cross-β fibril. We suggest mechanistic insights into the PSM functional amyloid formation and conformation transformation on the path from monomer-to-fibril formation. Details of PSMα1 assembly and fibril polymorphism suggest how utilizes functional amyloids to form biofilms and establish a framework for developing therapeutics against infection and antimicrobial resistance.
External linksProc Natl Acad Sci U S A / PubMed:39116134 / PubMed Central
MethodsEM (helical sym.)
Resolution3.5 Å
Structure data

43835

9atw

EMDB-43835, PDB-9atw:
Structure of biofilm-forming functional amyloid PSMa1 from Staphylococcus aureus
Method: EM (helical sym.) / Resolution: 3.5 Å

Source
  • staphylococcus aureus (bacteria)
KeywordsSTRUCTURAL PROTEIN / functional amyloid fibril / biofilm / bacterial biofilm / phenol soluble modulin alpha1 / PSMa1

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