Engineering a Hyperstable Outer Membrane Protein Ail Using Thermodynamic Design.

Development of viable therapeutics to effectively combat tier I pneumopathogens such as requires a thorough understanding of proteins vital for pathogenicity. The host invasion protein Ail, although indispensable for 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.

Interplay of protein primary sequence, lipid membrane, and chaperone in β-barrel assembly.

The outer membrane of a Gram-negative bacterium is a crucial barrier between the external environment and its internal physiology. This barrier is bridged selectively by β-barrel outer membrane proteins (OMPs). The in vivo folding and biogenesis of OMPs necessitates the assistance of the outer membrane chaperone BamA.