Signal transduction in photoreceptor histidine kinases

Abstract

Two‐component systems (TCS) constitute the predominant means by which prokaryotes read out and adapt to their environment. Canonical TCSs comprise a sensor histidine kinase (SHK), usually a transmembrane receptor, and a response regulator (RR). In signal‐dependent manner, the SHK autophosphorylates and in turn transfers the phosphoryl group to the RR which then elicits downstream responses, often in form of altered gene expression. SHKs also catalyze the hydrolysis of the phospho‐RR, hence, tightly adjusting the overall degree of RR phosphorylation. Photoreceptor histidine kinases are a subset of mostly soluble, cytosolic SHKs that sense light in the near‐ultraviolet to near‐infrared spectral range. Owing to their experimental tractability, photoreceptor histidine kinases serve as paradigms and provide unusually detailed molecular insight into signal detection, decoding, and regulation of SHK activity. The synthesis of recent results on receptors with light‐oxygen‐voltage, bacteriophytochrome and microbial rhodopsin sensor units identifies recurring, joint signaling strategies. Light signals are initially absorbed by the sensor module and converted into subtle rearrangements of α helices, mostly through pivoting and rotation. These conformational transitions propagate through parallel coiled‐coil linkers to the effector unit as changes in left‐handed superhelical winding. Within the effector, subtle conformations are triggered that modulate the solvent accessibility of residues engaged in the kinase and phosphatase activities. Taken together, a consistent view of the entire trajectory from signal detection to regulation of output emerges. The underlying allosteric mechanisms could widely apply to TCS signaling in general.

Signaling mechanism of phytochromes in solution

“…43 Coiled-coil interactions of the Cterminal extension of the helical spine to the output domain have been shown to be critical for controlling the signaling output in phytochromes, 58 resembling the converged view for other bacterial histidine kinases. 10,25 These considerations provide support for our proposed new pathway for signal transduction from the chromophore via the knot region to the lower part of the helical spine.…”

“…[53][54][55][56] Helical spines are common structural elements in many signaling proteins and critical for signal transduction. 10,24,25,57 While the helical spine exists in all phytochromes, the PHYtongue does not, because PHY-less phytochromes exist. 43 Coiled-coil interactions of the Cterminal extension of the helical spine to the output domain have been shown to be critical for controlling the signaling output in phytochromes, 58 resembling the converged view for other bacterial histidine kinases.…”

“…Many sensory proteins contain helical spines, where they are actively involved in signaling. 10,24,25 This also seems likely for phytochromes. 18,26 A bending of the spine in between the PAS-GAF and PHY domains has been inferred from crystal structures, X-ray solution scattering, and DEER spectroscopy (SI Appendix, Fig.…”

Illuminating a Phytochrome Paradigm – a Light-Activated Phosphatase in Two-Component Signaling Uncovered

“…In contrast to the typical transmembrane HK receptors, light sensitive receptors are frequently soluble. This facilitates their structural and mechanistic analyses 4,18,19 . As a case in point, phytochromes are red/far-red light-sensing photoreceptors that regulate diverse physiological processes in plants, fungi, and bacteria 20 , e.g., chromatic adaptation and phototaxis in prokaryotes 21 .…”

“…As a case in point, phytochromes are red/far-red light-sensing photoreceptors that regulate diverse physiological processes in plants, fungi, and bacteria 20 , e.g., chromatic adaptation and phototaxis in prokaryotes 21 . Bacterial phytochromes (BphPs) usually belong to two-component signaling systems, with a cognate response regulator commonly encoded in the same operon 18,22,23 . BphPs comprise an N-terminal photosensory module (PSM) with PAS (Period/ARNT/Single-minded), GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) and PHY (Phytochrome-specific) domains 24 .…”