Abstract
Prion-like proteins can switch between a soluble intrinsically disordered conformation and a highly ordered amyloid assembly. This conformational promiscuity is encoded in specific sequence regions, known as prion domains (PrDs). Prions are best known as the causative factors of neurological diseases in mammals. However, bioinformatics analyses reveal that proteins bearing PrDs are present in all kingdoms of life, including bacteria, thus supporting the idea that they serve conserved beneficial cellular functions. Despite the proportion of predicted prion-like proteins in bacterial proteomes is generally low, pathogenic species seem to have a higher prionic load, suggesting that these malleable proteins may favor pathogenic traits. In the present work, we performed a stringent computational analysis of the Clostridium botulinum pathogen proteome in the search for prion-like proteins. A total of 54 candidates were predicted for this anaerobic bacterium, including the transcription termination Rho factor. This RNA-binding protein has been shown to play a crucial role in bacterial adaptation to changing environments. We show here that the predicted disordered PrD domain of this RNA-binding protein contains an inner, highly polar, asparagine-rich short sequence able to spontaneously self-assemble into amyloid-like structures, bearing thus the potential to induce a Rho factor conformational switch that might rewire gene expression in response to environmental conditions.
Highlights
Amyloid forming proteins are found in all kingdoms of life, from Bacteria to Animalia (Fowler et al, 2007; Eichner and Radford, 2011; Sanchez de Groot et al, 2012)
Both PAPA and pWALTZ algorithms were trained on top of yeast prions; they are based on radically different concepts, a suitable composition of the prion-forming domains (PrDs) and the presence of an amyloid core embedded in it, respectively
Because many of the prion-like polypeptides identified in eukaryotes are RNA binding proteins (King et al, 2012; Kim et al, 2013), we focused our attention in the transcription termination factor Rho (Rho)
Summary
Amyloid forming proteins are found in all kingdoms of life, from Bacteria to Animalia (Fowler et al, 2007; Eichner and Radford, 2011; Sanchez de Groot et al, 2012). The conformational duality of prion-like proteins resides in structurally independent, low complexity, prion-forming domains (PrDs), usually enriched in asparagine (N) and glutamine (Q) residues (Dorsman et al, 2002; Fandrich and Dobson, 2002; Halfmann et al, 2011). This composition endorses the domains with intrinsic structural disorder, which enables selfassembly without a requirement for conformational unfolding (Fuxreiter, 2012; Malinovska et al, 2013). Ontology analysis indicates that PrD-containing proteins are associated with a great variety of physiological functions, supporting prion-like proteins acting as beneficial elements for organisms
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