Engineering a Hyperstable <i>Yersinia pestis</i> Outer Membrane Protein Ail Using Thermodynamic Design.

ABSTRACT: Development of viable therapeutics to effectively combat tier I pneumopathogens such as Yersinia pestis requires a thorough understanding of proteins vital for pathogenicity. The host invasion protein Ail, although indispensable for Yersinia pathogenesis, has evaded detailed characterization, as it is an outer membrane protein with intrinsically low stability and high aggregation propensity. Here, we identify molecular elements of the metastable Ail structure that considerably alter protein-lipid and intraprotein thermodynamics. In addition, we find that four residues Q⁵⁰, L⁸⁸, L⁹², and A⁹⁴ contribute additively to the lowered stability of Ail, and their conserved substitution is sufficient to re-engineer Ail to Out14, a thermodynam

SUBMITTER: George A 

PROVIDER: S-EPMC7612368 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature