6bo0 | pdb_00006bo0
MdbA protein, a thiol-disulfide oxidoreductase from Corynebacterium matruchotii
Structural highlights
FunctionPublication Abstract from PubMedThe actinobacterium Corynebacterium matruchotii has been implicated in nucleation of oral microbial consortia leading to biofilm formation. Due to the lack of genetic tools, little is known about basic cellular processes, including protein secretion and folding, in this organism. We report here a survey of the C. matruchotii genome, which encodes a large number of exported proteins containing paired cysteine residues, and identified an oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA (MdbACd). Crystallization studies uncovered that the 1.2-A resolution structure of C. matruchotii MdbA (MdbACm) conforms two conserved features found in actinobacterial MdbA enzymes, a thioredoxin-like fold and an extended alpha-helical domain. By reconstituting disulfide bond-forming machine in vitro, we demonstrated that MdbACm catalyzes disulfide bond formation within the actinobacterial pilin FimA. A new gene deletion method supported that mdbA is essential in C. matruchotii Remarkably, heterologous expression of MdbACm in the Cdiphtheriae DeltamdbA mutant rescued its known defects in cell growth and morphology, toxin production, and pilus assembly, and this thiol-disulfide oxidoreductase activity required the catalytic motif CXXC. Altogether, the results suggest that MdbACm is a major thiol-disulfide oxidoreductase, which likely mediates post-translocational protein folding in C. matruchotii by a mechanism that is conserved in Actinobacteria.IMPORTANCE The actinobacterium Corynebacterium matruchotii has been implicated in the development of oral biofilms or dental plaque; however, little is known about the basic cellular processes in this organism. We report here a high-resolution structure of a C. matruchotii oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA. By biochemical analysis, we demonstrated that C. matruchotii MdbA catalyzes disulfide bond formation in vitro Furthermore, a new gene deletion method revealed that deletion of mdbA is lethal in C. matruchotii Remarkably, C. matruchotii MdbA can substitute C. diphtheriae MdbA to maintain normal cell growth and morphology, toxin production, and pilus assembly. Overall, our studies support that C. matruchotii utilizes MdbA as a major oxidoreductase to catalyze oxidative protein folding. Structural basis of a thiol-disulfide oxidoreductase in the hedgehog-forming actinobacterium Corynebacterium matruchotii.,Luong TT, Tirgar R, Reardon-Robinson M, Joachimiak A, Osipiuk J, Ton-That H J Bacteriol. 2018 Feb 12. pii: JB.00783-17. doi: 10.1128/JB.00783-17. PMID:29440253[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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