The PEB4 protein is an antigenic virulence factor implicated in host cell adhesion, invasion, and colonization in the foodborne pathogen Campylobacter jejuni. peb4 mutants have defects in outer membrane protein assembly and PEB4 is thought to act as a periplasmic chaperone. The crystallographic structure of PEB4 at 2.2-Å resolution reveals a dimer with distinct SurA-like chaperone and peptidyl-prolyl cis/trans isomerase (PPIase) domains encasing a large central cavity. Unlike SurA, the chaperone domain is formed by interlocking helices from each monomer, creating a domain-swapped architecture. PEB4 stimulated the rate of proline isomerization limited refolding of denatured RNase T 1 in a juglone-sensitive manner, consistent with parvulin-like PPIase domains. Refolding and aggregation of denatured rhodanese was significantly retarded in the presence of PEB4 or of an engineered variant specifically lacking the PPIase domain, suggesting the chaperone domain possesses a holdase activity. Using bioinformatics approaches, we identified two other SurA-like proteins (Cj1289 and Cj0694) in C. jejuni. The 2.3-Å structure of Cj1289 does not have the domain-swapped architecture of PEB4 and thus more resembles SurA. Purified Cj1289 also enhanced RNase T 1 refolding, although poorly compared with PEB4, but did not retard the refolding of denatured rhodanese. Structurally, Cj1289 is the most similar protein to SurA in C. jejuni, whereas PEB4 has most structural similarity to the Par27 protein of Bordetella pertussis. Our analysis predicts that Cj0694 is equivalent to the membrane-anchored chaperone PpiD. These results provide the first structural insights into the periplasmic assembly of outer membrane proteins in C. jejuni.

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Peroxisomes are dynamic organelles essential for optimum functioning of a eukaryotic cell. Biogenesis of these organelles and the diverse functions performed by them have been extensively studied in the past decade. Their ability to perform functions depending on the cell type and growth conditions is unique and remarkable. Oxidation of fatty acids and reactive oxygen species metabolism are the two most important functions of these ubiquitous organelles. They are often referred to as both source and sink of reactive oxygen species in a cell. Recent research connects peroxisome dysfunction to fatal oxidative damage associated with ageing-related diseases/disorders. It is now widely accepted that mitochondria and peroxisomes are required to maintain oxidative balance in a cell. However, our understanding on the inter-dependence of these organelles to maintain cellular homeostasis of reactive oxygen species is still in its infancy. Herein, we summarize findings that highlight the role of peroxisomes in cellular reactive oxygen species metabolism, ageing and age-related disorders.

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