SURA

SurA is a periplasmic chaperone and peptidyl-prolyl isomerase (PPIase) found in many Gram-negative bacteria, most extensively studied in Escherichia coli. It plays a central role in outer membrane protein (OMP) biogenesis by binding to unfolded or partially folded OMPs in the periplasm, preventing aggregation, and guiding them toward the beta-barrel assembly machine (Bam complex) for proper insertion into the outer membrane.

Localization and maturation: SurA is synthesized with an N-terminal signal peptide that directs export across the inner membrane via the Sec pathway. The signal peptide is cleaved to yield the mature, periplasmic protein.

Structure: SurA has a modular architecture consisting of an N-terminal core domain, two peptidyl-prolyl isomerase (PPIase) domains (PPIase I and II) of FKBP-like fold, and a C-terminal domain. This arrangement forms a flexible cradle that engages unfolded OMP substrates. While PPIase activity can assist proline isomerization, the chaperone function of SurA appears at least partly independent of catalysis.

Function and interactions: SurA operates in concert with other periplasmic chaperones such as Skp and the Bam complex. It helps maintain OMPs in a folding-competent state and delivers them to BamA for insertion into the outer membrane. Defects in SurA lead to accumulation of misfolded OMPs, increased outer membrane permeability, and heightened sensitivity to detergents and antibiotics.

Distribution and significance: SurA is conserved in many Gram-negative bacteria and is a key component of the envelope biogenesis pathway. Its essential role in OMP assembly has made it of interest as a potential target for antimicrobial strategies.