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

Midgett, Charles R.; Swindell, Rachel A.; Pellegrini, Maria; Jon Kull, F.

doi:10.1038/s41598-020-66050-5

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

Journal Article · Tue Jun 02 00:00:00 EDT 2020 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-020-66050-5· OSTI ID:1816255

Midgett, Charles R. ^[1]; Swindell, Rachel A. ^[1]; Pellegrini, Maria ^[1]; Jon Kull, F. ^[1]

Dartmouth College, Hanover, NH (United States). Dept. of Chemistry

ToxR is a transmembrane transcription factor that, together with its integral membrane periplasmic binding partner ToxS, is conserved across the Vibrionaceae 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 Vibrionaceae family.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; USDOE Office of Science (SC), Biological and Environmental Research (BER); NIAID; BioMT COBRE; National Institutes of Health (NIH)

Grant/Contract Number:: SC0012704; R21-AI140740; P20-GM113132; P30GM133893; KP1605010

OSTI ID:: 1816255

Journal Information:: Scientific Reports, Vol. 10, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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x-ray crystallography

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

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References (47)

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