Structural and functional characterization of three DsbA paralogues from Salmonella enterica serovar typhimurium.
In prototypic Escherichia coli K-12 the introduction of disulfide bonds into folding proteins is mediated by the Dsb family of enzymes, primarily through the actions of the highly oxidizing protein EcDsbA. Homologues of the Dsb catalysts are found in most bacteria. Interestingly, pathogens have developed distinct Dsb machineries that play a pivotal role in the biogenesis of virulence factors, hence contributing to their pathogenicity. Salmonella enterica serovar (sv.) Typhimurium encodes an extended number of sulfhydryl oxidases, namely SeDsbA, SeDsbL, and SeSrgA. Here we report a comprehensive analysis of the sv. Typhimurium thiol oxidative system through the structural and functional characterization of the three Salmonella DsbA paralogues. The three proteins share low sequence identity, which results in several unique three-dimensional characteristics, principally in areas involved in substrate binding and disulfide catalysis. Furthermore, the Salmonella DsbA-like proteins also have different redox properties. Whereas functional characterization revealed some degree of redundancy, the properties of SeDsbA, SeDsbL, and SeSrgA and their expression pattern in sv. Typhimurium indicate a diverse role for these enzymes in virulence.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia. b.heras@imb.uq.edu.au
Begoña
B
Heras
Makrina
M
Totsika
Russell
R
Jarrott
Stephen R
SR
Shouldice
Gregor
G
Guncar
Maud E S
ME
Achard
Timothy J
TJ
Wells
M Pilar
MP
Argente
Alastair G
AG
McEwan
Mark A
MA
Schembri
D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000737:chemistry; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000737:chemistry*; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012486:Salmonella typhimurium / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction
D004220:Disulfides; D029968:Escherichia coli Proteins; D005978:Glutathione; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D019704:Protein Disulfide-Isomerases; C526648:dsbA protein, E coli