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bioRxiv · 10.1101/2020.02.24.963330

A disulfide constrains the ToxR periplasmic domain structure, altering its interactions with ToxS and bile-salts

Midgett, C. R.·Swindell, R. A.·Pellegrini, M.·Kull, F. J.
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Abstract

ToxR is a transmembrane transcription factor that, together with its integral membrane periplasmic binding partner ToxS, is conserved across the Vibrio family. In some pathogenic Vibrios, including V. parahaemolyticus and V. cholerae, ToxR is required for bile resistance and virulence, and ToxR is fully activated and protected from degradation by ToxS. ToxS achieves this in part by ensuring formation of an intra-chain disulfide bond in the C-terminal periplasmic domain of ToxR (dbToxRp). In this study, biochemical analysis showed dbToxRp to have a higher affinity for the ToxS periplasmic domain than the non-disulfide bonded conformation. Analysis of our dbToxRp crystal structure showed this is due to disulfide bond stabilization. Furthermore, dbToxRp is structurally homologous to the V. parahaemolyticus VtrA periplasmic domain. These results highlight the critical structural role of disulfide bond in ToxR and along with VtrA define a domain fold involved in environmental sensing conserved across the Vibrio family.

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Midgett, C. R., Swindell, R. A., Pellegrini, M., Kull, F. J.. 2020-02-25. A disulfide constrains the ToxR periplasmic domain structure, altering its interactions with ToxS and bile-salts. https://doi.org/10.1101/2020.02.24.963330

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