5C00

MdbA protein, a thiol-disulfide oxidoreductase from Corynebacterium diphtheriae

Summary for 5C00

• Entry DOI: 10.2210/pdb5c00/pdb
• Descriptor: MdbA protein (2 entities in total)
• Functional Keywords: mdba, dip1880, thiol-disulfide oxidoreductase, structural genomics, midwest center for structural genomics, mcsg, psi-biology, oxidoreductase
• Biological source: Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
• Total number of polymer chains: 4
• Total formula weight: 91187.44

Authors

OSIPIUK, J.,REARDON-ROBINSON, M.E.,TON-THAT, H.,JOACHIMIAK, A.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2015-06-11, release date: 2015-07-15, Last modification date: 2024-11-06)

Primary citation

Reardon-Robinson, M.E.,Osipiuk, J.,Jooya, N.,Chang, C.,Joachimiak, A.,Das, A.,Ton-That, H.
A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.
Mol.Microbiol., 98:1037-1050, 2015

PubMed Abstract: The 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 suggests 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 cysteines 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 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 ΔmdbA 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.

PubMed: 26294390
DOI: 10.1111/mmi.13172

Experimental method

X-RAY DIFFRACTION (1.77 Å)