Molecular model of a sensor of two-component signaling system

This study is about Two-component systems (TCS) that are widespread signaling systems present in all domains of life. TCS typically consist of a signal receptor/transducer and a response regulator. The receptors (histidine kinases, chemoreceptors and photoreceptors) are often embedded in the membrane and have a similar modular structure. Chemoreceptors were shown to function in highly ordered arrays, with trimers of dimers being the smallest functional unit. However, much less is known about photoreceptors. Here, we use small-angle scattering (SAS) to show that detergent-solubilized sensory rhodopsin II in complex with its cognate transducer forms dimers at low salt concentration, which associate into trimers of dimers at higher buffer molarities.

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Fig: Signal transduction pathway in case of the two-component phototaxis system of Natronomonas pharaonis5 and domain architecture of membrane chemo- and photoreceptors of TCS. (A) Light activated sensory rhodopsin II (NpSRII) induces conformational and/or dynamical changes in the transducer (NpHtrII), which are converted by two HAMP domains and conveyed along the 200 Å long transducer to the tip region. Activated by the transducer histidine kinase CheA (bound to the adapter protein CheW) undergoes auto-phosphorylation and further transfers the phosphate group to the response regulators CheY or CheB. CheY affects the rotational bias of the flagellar motor, while the methylesterase CheB along with the methyltransferase CheR controls the adaptation mechanism. (B) Cartoon representations of the chemoreceptor dimer (Tar and Tsr in complex with kinases) from E. coli and of the photosensor dimer of the complex of the sensory rhodopsin II with its cognate transducer NpHtrII and kinases from N. pharaonis.

We then fit an atomistic model of the whole complex into the SAS data. The obtained results suggest that the trimer of dimers is “tripod”-shaped and that the contacts between the dimers occur only through their cytoplasmic regions, whereas the transmembrane regions remain unconnected.

Ryzhykau, Y.L., Orekhov, P.S., Rulev, M.I. et al. Molecular model of a sensor of two-component signaling system. Sci Rep 11, 10774 (2021). https://doi.org/10.1038/s41598-021-89613-6

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