What can AlphaFold do for antimicrobial amyloids?

Amyloids, protein, and peptide assemblies in various organisms are crucial in physiological and pathological processes. Their intricate structures, however, present significant challenges, limiting our understanding of their functions, regulatory mechanisms, and potential applications in biomedicine and technology. This study evaluated the AlphaFold2 ColabFold method's structure predictions for antimicrobial amyloids, using eight antimicrobial peptides (AMPs), including those with experimentally determined structures and AMPs known for their distinct amyloidogenic morphological features.

Sticking to the Subject: Multifunctionality in Microbial Adhesins.

Bacterial and fungal adhesins mediate microbial aggregation, biofilm formation, and adhesion to host. We divide these proteins into two major classes: professional adhesins and moonlighting adhesins that have a non-adhesive activity that is evolutionarily conserved. A fundamental difference between the two classes is the dissociation rate.

Natural Antimicrobial Peptides Self-assemble as α/β Chameleon Amyloids.

Amyloid protein fibrils and some antimicrobial peptides (AMPs) share biophysical and structural properties. This observation suggests that ordered self-assembly can act as an AMP-regulating mechanism, and, vice versa, that human amyloids play a role in host defense against pathogens, as opposed to their common association with neurodegenerative and systemic diseases. Based on previous structural information on toxic amyloid peptides, we developed a sequence-based bioinformatics platform and, led by its predictions, experimentally identified 14 fibril-forming AMPs (ffAMPs) from living organisms, which demonstrated cross-β and cross-α amyloid properties.

Rare by Natural Selection: Disulfide-Bonded Supramolecular Antimicrobial Peptides.

Human LL-37 is an antimicrobial peptide forming thermostable supramolecular fibrils that surround bacterial cells. The crystal structure of LL-37 bearing an I24C substitution of most buried position in the fibril revealed disulfide-bonded dimers that further assembled into a fibrillar structure of densely packed helices We further demonstrated the position-dependent controllable antibacterial activity of LL-37 I24C and other cysteine mutants, mediated by regulation of intermolecular disulfide bonds and their role in the formation of supramolecular structures. The morphology of the fibrils and their antibacterial mechanism of action might be dependent on their interactions with specific bacteria.

Functional and pathological amyloid structures in the eyes of 2020 cryo-EM.

The amyloid state of protein aggregation is associated with neurodegenerative and systemic diseases but can play physiological roles in many organisms, including as stress granules and virulence determinants. The recent resolution revolution in cryogenic electron microscopy (cryo-EM) has significantly expanded the repertoire of high-resolution amyloid structures, to include, for the first-time, fibrils extracted ex vivo in addition to those formed, or seeded, in vitro. Here, we review recently solved cryo-EM amyloid structures, and compare amino acid prevalence, in efforts to systematically distinguish between pathological and functional amyloids, even though such structural classification is hindered by extensive polymorphism even among fibrils of the same protein, and by dual functioning of some human amyloids in both physiological activities and disease mechanisms.