6c29

Publication Abstract from PubMed

Correct disulfide bond formation is essential for proper folding of many proteins, including bacterial virulence factors. The suppressor of copper sensitivity (Scs) proteins have roles in dithiol/disulfide interchange and the bacterial response to copper stress. Encoded in a four-gene cassette (ScsABCD) present in many Gram-negative bacteria, the Scs proteins are enigmatic and poorly characterised. Here, we show that the periplasmic alpha domain of the membrane protein ScsB in the Gram-negative bacterium Proteus mirabilis forms a redox relay with the soluble periplasmic protein PmScsC. We also found that the periplasmic alpha domain is sufficient to activate the disulfide isomerase activity of PmScsC. The crystal structure of PmScsBalpha at a resolution of 1.54 A revealed that it comprises two structurally similar immunoglobulin-like folds, one of which includes a putative redox-active site with the sequence CXXXC. We confirmed the importance of these cysteine residues for PmScsBalpha function and engineered cysteine variants that produced a stable complex between PmScsC and PmScsBalpha. Using small-angle X-ray and neutron scattering analyses with contrast variation, we determined a low-resolution structure of the PmScsC-PmScsBalpha complex. The structural model of this complex suggested that PmScsBalpha uses both of its immunoglobulin-like folds to interact with PmScsC and also revealed that the highly dynamic PmScsC becomes ordered upon PmScsBalpha binding. These findings add to our understanding of the poorly characterised Scs proteins.

Disulfide isomerase activity of the dynamic, trimeric Proteus mirabilis ScsC protein is primed by the tandem immunoglobulin-fold domain of ScsB.,Furlong EJ, Choudhury HG, Kurth F, Duff AP, Whitten AE, Martin JL J Biol Chem. 2018 Feb 28. pii: RA118.001860. doi: 10.1074/jbc.RA118.001860. PMID:29491145^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.