Structural highlights
FunctionPublication Abstract from PubMedThe Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggest the existence of an oxidative protein-folding pathway in this organism. Here, we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteins abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved a thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the DeltamdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production, and virulence.,Reardon-Robinson ME, Osipiuk J, Jooya N, Chang C, Joachimiak A, Das A, Ton-That H Mol Microbiol. 2015 Aug 21. doi: 10.1111/mmi.13172. PMID:26294390[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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