FkpA

FkpA is a periplasmic folding catalyst found in many Gram-negative bacteria, most notably Escherichia coli. It is directed to the periplasm by a Sec-dependent signal peptide and typically functions as a homodimer in this compartment. In the periplasm, FkpA contributes to proper protein folding under normal and stress conditions, assisting the maturation of envelope and secreted proteins.

Structurally, FkpA comprises two functional domains: an N-terminal dimerization domain and a C-terminal FKBP-like peptidyl-prolyl cis-trans isomerase (PPIase) domain. The FKBP domain belongs to the FKBP family of PPIases and can accelerate cis-trans isomerization of proline residues, while the N-terminal region mediates dimerization and influences chaperone activity. The protein exhibits dual functionality, acting both as a chaperone that prevents aggregation of unfolded polypeptides and as a PPIase that catalyzes proline isomerization.

In vivo, FkpA supports the correct folding of a range of periplasmic and outer membrane proteins, including some outer membrane proteins. It operates alongside other periplasmic chaperones such as SurA, Skp, and DegP to facilitate envelope protein assembly. FkpA is particularly important under envelope stress or when folding substrates are challenging, contributing to cellular fitness when secretory or membrane protein synthesis is high.

In research contexts, FkpA serves as a model of a dual-function chaperone–PPIase and is used to study protein folding in the bacterial periplasm. While not always essential for growth under standard laboratory conditions, its absence can compromise folding efficiency and stress resilience, highlighting its role in maintaining periplasmic proteostasis.