What is it about?
We have studied a PSMα1 protein from the infectious bacteria Staphylococcus aureus, which is known for forming protective layers called biofilms. Using a technique called cryo-EM, we discovered how PSMα1 proteins come together to form long, helical amyloid fibrillar structures. 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 C2-symmetric U-shaped protofilaments whose subunits are unusually tilted out-of-plane. Remarkably, the monomeric α-helical PSMα1 is extremely cytotoxic to cells, despite the moderate toxicity of the cross-β fibril. Overall with this novel structure, we could suggest mechanistic insights into the PSM functional amyloid formation and conformation transformation on the path from monomer-to-fibril formation, which is a key process in the S. aureus biofilm formation and pathogenicity.
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Photo by National Institute of Allergy and Infectious Diseases on Unsplash
Why is it important?
The PSMa1 structure is extremely important because, even though many similar proteins have been studied before, this is the first time scientists have gotten such a detailed look at how these specific biofilm-forming proteins build their structure. Importantly, understanding this can help in developing new ways to fight bacterial infections, especially those that are resistant to current treatments.
Perspectives
Details of PSMα1 assembly and fibril polymorphism suggest how S. aureus utilizes functional amyloids to form biofilms and establish a framework for developing therapeutics against infection and antimicrobial resistance. Our findings show that the PSMα1 structure and fibrilization initiation model we present here provide a critical structural and mechanistic understanding of the functional amyloid biogenesis in pathogenic S. aureus biofilm formation and suggest mechanistic insights. This information could lead to the development of anti-biofilm and anti-amyloid therapeutics to fight biofilm-related antimicrobial resistance.
Umit Akbey
University of Pittsburgh
Read the Original
This page is a summary of: Structure of biofilm-forming functional amyloid PSMα1 from
Staphylococcus aureus, Proceedings of the National Academy of Sciences, August 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2406775121.
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