Department of Chemistry, Dartmouth College, Hanover, NH, USA.
Sci Rep. 2020 Jun 2;10(1):9002. doi: 10.1038/s41598-020-66050-5.
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.
ToxR 是一种跨 Vibionaceae 家族保守的跨膜转录因子，与它的完整膜周质结合伴侣 ToxS 一起。在一些致病性弧菌中，包括副溶血性弧菌和霍乱弧菌，ToxR 是耐胆汁和毒力所必需的，ToxR 被 ToxS 完全激活并免受降解。ToxS 通过确保 ToxR （dbToxRp）C 末端周质域内形成一个链内二硫键来实现这一点。在这项研究中，生化分析表明 dbToxRp 与非二硫键结合构象相比，对 ToxS 周质域具有更高的亲和力。我们对 dbToxRp 晶体结构的分析表明，这是由于二硫键的稳定作用。此外，dbToxRp 在结构上与副溶血性弧菌的 VtrA 周质域同源。这些结果突出了二硫键在 ToxR 中的关键结构作用，并与 VtrA 一起定义了 Vibionaceae 家族中保守的环境感应相关的结构折叠域。
