Sequential conformational transitions and α-helical supercoiling regulate a sensor histidine kinase

Abstract

Sensor histidine kinases are central to sensing in bacteria and in plants. They usually contain sensor, linker, and kinase modules and the structure of many of these components is known. However, it is unclear how the kinase module is structurally regulated. Here, we use nano- to millisecond time-resolved X-ray scattering to visualize the solution structural changes that occur when the light-sensitive model histidine kinase YF1 is activated by blue light. We find that the coiled coil linker and the attached histidine kinase domains undergo a left handed rotation within microseconds. In a much slower second step, the kinase domains rearrange internally. This structural mechanism presents a template for signal transduction in sensor histidine kinases.

Signal transduction in photoreceptor histidine kinases

“…Due to the entangling of the A′α helices, complete dissociation of the LOV monomers is prevented. As recently demonstrated, the weakening of the β‐sheet:A′α interaction is rather channeled into a slight rotation and tilting apart of the monomers (Figure d). This quaternary transition entails a separation of the Jα anchor sites at the tips of the Iβ strands by around 3 å which provides the mechanistic basis for signal propagation to the linker and the histidine kinase effector unit, see below.…”

“…To fully unravel signal‐dependent conformational transitions of the linker, one would ideally require atomically resolved structural information on the same SHK for different functional states. Although structural data of that type are not available yet, the conformational transitions that the YF1 SHK undergoes upon blue‐light absorption were recently charted by EPR spectroscopy and X‐ray solution diffraction . The time‐resolved scattering data revealed a biphasic response of full‐length YF1 to light absorption.…”

“…Although structural data of that type are not available yet, the conformational transitions that the YF1 SHK undergoes upon blue-light absorption were recently charted by EPR spectroscopy 74 and X-ray solution diffraction. 75,76 The time-resolved scattering data revealed a biphasic response of full-length YF1 to light absorption. A fast phase, rate-limited by photochemical events within the LOV photosensor, see above, occurs on the microsecond scale and is followed by a much slower phase on the millisecond scale.…”

“…The structural changes manifest within the LOV sensor after blue‐light absorption in a single concerted step on the microsecond timescale, synchronously with thioadduct formation. Notably, consistent light‐induced conformational transitions have been observed by two independent experimental techniques (double electron–electron resonance [DEER] spectroscopy and X‐ray solution scattering), and in the context of either the isolated Bs YtvA photosensor or the composite LOV‐SHK YF1. These findings not only confirm the observed signaling mode, but also they imply that this mode is little affected by C‐terminal appendage of an effector module.…”

“…(a) Blue‐light absorption triggers increased left‐handed supercoiling of the coiled‐coil linker of YF1 and thereby switches the receptor from the K to the P state. Viewed along the C 2 axis of the receptor from C to N terminus, left‐handed supercoiling of the linker would translate into global left‐handed twist of the receptor (indicated by the arrows), as indeed determined by X‐ray solution scattering and molecular modeling . (b) In case of the Deinococcus radiodurans BPhy histidine kinase, solution scattering indicates that red light triggers a right‐handed twist of the receptor.…”