Structural and DNA-binding properties of the cytoplasmic domain of Vibrio cholerae transcription factor ToxR

Abstract

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ToxR activates the Vibrio cholerae virulence genes by tethering DNA to the membrane through versatile binding to multiple sites

“…The segment comprising helices α2 and α3 forms a modified winged helix-turn-helix DNA-binding motif (wHTH) ( 35 ), with α2-α3 connector (α-loop or transactivation loop) replacing the turn. The structure is similar, although not identical, to the recently reported NMR model of ToxR not bound to DNA (PDB ID: 7NMB) ( 36 ) (rmsd = 2.94 Å). The main differences are located at the α-loop and at the segment connecting helix α3 with the wing (ancillary wing region) ( SI Appendix , Fig.…”

Vibrio cholerae’sToxRS Bile Sensing System

“…A distinctive feature of members of the 'ToxR-like' transcription factor family is the transduction of signals through the membrane without chemical modification, probably via conformational changes (Eichinger et al, 2011;Gubensäk et al, 2021a;Kenney, 2002;Martínez-Hackert and Stock, 1997a;Martínez-Hackert and Stock, 1997b). Thus, we suggest that the observed structural changes of the periplasmic domains of ToxRS upon bile recognition are passed on through the ToxR transmembrane domain to its cytoplasmic effector domain, thereby enhancing ToxR binding to recognition sequences and subsequently induction of transcription (Fig.…”

“…S1) involved in the regulation of numerous genes, not only virulence associated, and can function as an activator, co-activator and repressor (Bina et al, 2003;Champion et al, 1997;Lee et al, 2000;Morgan et al, 2011;Skorupski and Taylor, 1997;Wang et al, 2002;Welch and Bartlett, 1998). ToxR periplasmic domain is proposed to act as environmental sensor, being able to bind to bile acids with its periplasmic domain (Midgett et al, 2017;Midgett et al, 2020) and consequently activate transcription with its cytoplasmic DNA binding domain (Gubensäk et al, 2021a;Morgan et al, 2011;Morgan et al, 2019;Pfau and Taylor, 1996;Withey and DiRita, 2006), thus inducing a switch of outer membrane proteins from OmpT to OmpU (Simonet et al, 2003;Wibbenmeyer et al, 2002). Since OmpU is more efficient in excluding bile salts due to its negatively charged pore (Duret and Delcour, 2006;Simonet et al, 2003), bile-induced ToxR activation enables V. cholerae survival in the human gut (Wibbenmeyer et al, 2002).…”