Motifs and interface amino acid-mediated regulation of amyloid biogenesis in microbes to humans: potential targets for intervention.

Amyloids are linked to many debilitating diseases in mammals. Some organisms produce amyloids that have a functional role in the maintenance of their biological processes. Microbes utilize functional bacterial amyloids (FuBA) for pathogenicity and infections. Amyloid biogenesis is regulated differentially in various systems to avoid its toxic accumulation. A familiar feature in the process of amyloid biogenesis from humans to microbes is its regulation by protein-protein interactions (PPI). The spatial arrangement of amino acid residues in proteins generates topologies like flat interface and linear motif, which participate in protein interactions. Motifs and interface residue-mediated interactions have a direct or an indirect impact on amyloid secretion and assembly. Some motifs undergo post-translational modifications (PTM), which effects interactions and dynamics of the amyloid biogenesis cascade. Interaction-induced local changes stimulate global conformational transitions in the PPI complex, which indirectly affects amyloid formation. Perturbation of such motifs and interface residues results in amyloid abolishment. Interface residues, motifs and their respective interactive protein partners could serve as potential targets for intervention to inhibit amyloid biogenesis.