Prediction of Prion Proteins in E. coli Based on Bimodal Sequence Characteristics.

Authors

Katherine Shreeve, Jinoh Jang, Mridula Srivathsan, Siyu Li, Taylor D Scott, Silvia Cavagnero

Published in

Proteins. Aug 23, 2026. Epub Aug 23, 2026.

Abstract

Prions are infectious proteins that bear misfolded conformations capable of converting folded states into misfolded aggregates under physiologically relevant conditions. In mammals, prions cause deadly maladies including Creutzfeldt-Jakob and chronic wasting disease. To date, several prion proteins have been identified in eukaryotes, primarily vertebrates and fungi. There are, however, very few established prions in bacteria. Interestingly, the sequence of most vertebrate and yeast prions has bimodal characteristics. Namely, it comprises one intrinsically disordered and one folded region of comparable size. Here, we took advantage of this property to develop the PUFF algorithm, which can computationally identify Protein Unfolding/Folding Frameworks based on amino-acid sequence alone. After extensive validations with known prions from different organisms, we employed PUFF to predict juxtaposed intrinsically disordered and folded large regions across the E. coli proteome. Based on this criterion, PUFF predicted the presence of 102 novel 1st-generation prions. Additional analysis, taking sub-cellular compartmentalization and tryptophan distribution into account, led to establishing a refined group of 6 cytoplasmic 2nd-generation prion candidates. Some of these have unknown functions, while others are experimentally well-characterized proteins that are primarily involved in gene expression but were not previously flagged as prions. This study enhances our understanding of the E. coli-genome nature and suggests the existence of specific and experimentally testable novel prions in this organism. In all, our work moves a step forward towards the identification of new prions in bacteria.

PMID:
42633647
Bibliographic data and abstract were imported from PubMed on 24 Aug 2026.

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