Cover Picture: ChemBioChem 4/2002

Abstract

The cover picture shows a representation of a ratchet model where the integration of multiple signals by the transmitter kinase VirA is achieved by xenognostic signal induced movement between three accessible homodimeric coiled-coil interfaces. It is this interface registry that activates the kinase domain, initiating lateral gene transfer from Agrobacterium tumefaciens to its eukaryotic host. Further details can be found in the article by Lynn and co-workers on p. 311 ff.

A Rhizobium radiobacter Histidine Kinase Can Employ Both Boolean AND and OR Logic Gates to Initiate Pathogenesis

“…Chimeric constructs of VirA that bias the relative positions of the a4h elices of the GAF domain [3,24] led to the argument for www.chembiochem.org ap henol-induced twisting and as ugar-induced piston motion resultingi nacombined screw turn helical motion for activation. [1,32] As shown in Figure 8A,t he Tyr293s idec hain is positioned between the a1a nd a4h elices, the enteringa nd exiting heliceso fG AF,a nd at the 4-helix bundlei nterfaceo ft he active VirA dimer.T he polar Glu295 and Glu299 residues on a1 have been implicated in pistoning in response to sugar inputs. [1,25,32] Tyr293 might span the helical interface to Glu425 and Glu430 on a4; switching hydrogen bonding partners could result in twistingm otions.…”

“…[1,32] As shown in Figure 8A,t he Tyr293s idec hain is positioned between the a1a nd a4h elices, the enteringa nd exiting heliceso fG AF,a nd at the 4-helix bundlei nterfaceo ft he active VirA dimer.T he polar Glu295 and Glu299 residues on a1 have been implicated in pistoning in response to sugar inputs. [1,25,32] Tyr293 might span the helical interface to Glu425 and Glu430 on a4; switching hydrogen bonding partners could result in twistingm otions. Given the striking impact of substitutions in this region on phenol structural specificity and the polar nature of this site, we propose that exogenousp henols compete with Tyr293 hydrogen bondingt or elease crosshelical locking.…”

“…It appears that, as compensation for the low constitutive VirAc oncentration in strains Ag162,A B2/73, and KU12, the presence of ap henylalanine at 293 appropriately elevates the signalingr esponse. Strain KU12, moreover, containsadifferent phenol sensing profile; [1,14,27,32] this broadens the structuralr ange of inducing signals and might contributet oi ts successa sawide-host-range pathogen. Additionally, there are differences between the nature of aa299 as it relatest oh ostr ange (Figure6A).…”

“…[22,31] Specifically,t he presence of a vir box, an operator region that can be up-regulated by VirG, was shown to broaden the hostr ange. [3,23] This vir boxi sp resenti ns trains A6 and C58, but is absenti ns trains Ag162,A B2/73, andK U12 [1,23,32] (Figure S3). It appears that, as compensation for the low constitutive VirAc oncentration in strains Ag162,A B2/73, and KU12, the presence of ap henylalanine at 293 appropriately elevates the signalingr esponse.…”