Mechanism of Regulation of Receptor Histidine Kinases

Abstract

Bacterial transmembrane receptors regulate an intracellular catalytic output in response to extracellular sensory input. To investigate the conformational changes that relay the regulatory signal, we have studied the HAMP domain, a ubiquitous intracellular module connecting input to output domains. HAMP forms a parallel, dimeric, four-helical coiled coil, and rational substitutions in our model domain (Af1503 HAMP) induce a transition in its interhelical packing, characterized by axial rotation of all four helices (the gearbox signaling model). We now illustrate how these conformational changes are propagated to a downstream domain by fusing Af1503 HAMP variants to the DHp domain of EnvZ, a bacterial histidine kinase. Structures of wild-type and mutant constructs are correlated with ligand response in vivo, clearly associating them with distinct signaling states. We propose that altered recognition of the catalytic domain by DHp, rather than a shift in position of the phospho-accepting histidine, forms the basis for regulation of kinase activity.

Role of the PAS Sensor Domains in the Bacillus subtilis Sporulation Kinase KinA

“…Two-headed arrows indicate the movements that may lead to HK activation and deactivation. These are (i) 26°helical rotations of ␣2 against ␣1, as shown previously for EnvZ by Ferris et al (52), and (ii) "helix cracking" in ␣2 proposed previously for KinA by Dago et al (51 (Fig. 5), via a parallel or antiparallel alignment.…”

Dynamic Structural Changes Underpin Photoconversion of a Blue/Green Cyanobacteriochrome between Its Dark and Photoactivated States

“…Such rearrangements in TePixJ could affect the GAF domain dimerization contact, loosen constraints on the flanking HAMP domains imposed by the GAF domain as Pb, and/or reorient the HAMP domains relative to the GAF domain via movement or axial rotation of the ␣1/␣5 helical bundles. With respect to the latter possibility, it has been proposed that HAMP domain-containing kinases, in particular, couple ligand binding by the sensory domain to rotation of the HAMP domain helical bundles via a gear box-type mechanism (36). Notably, similar rearrangements could underpin signaling by phytochromes in general.…”

Phytochromes: An Atomic Perspective on Photoactivation and Signaling

“…For Te-PixJ, a light-driven swivel of the GAF domain helical bundle involved in dimerization could trigger rotation of the connected helical bundles found in its flanking HAMP domains (Cornilescu et al, 2014). Consequently, this CBCR could activate signaling through the gear box-type mechanism predicted for other HAMP domain-containing sensory receptors (Ferris et al, 2012).…”