2017年5月26日(金)
In the absence of a high-resolution structure
Our ELDOR experiments on YF1 H22P with inverted signal response revealed a drastically altered LOV photosensor dimer interface. The N-terminal A’α helices that in the original YF1 are embraced by the two LOV photosensors (Fig. 1A) and that play important roles in signal propagation and modulation19, 20 are displaced and possibly unstructured in H22P. As unequivocally demonstrated by ELDOR distance measurements on photo-induced NSQ radicals of the FMN chromophores, the two LOV photosensors in H22P are much closer in distance than in the original YF1. The observed distance between the two NSQ perfectly agrees with a flush packing of the LOV domains against another via their β sheets. Strikingly, this altered quaternary structure largely corresponds to the arrangement in an earlier structure of the isolated BsYtvA LOV domain that entirely lacked the A’α helices. Given its completely altered dimer interface, it is perplexing that the H22P variant still transduces LED Filament Bulbsignals, and even more so, in inverted manner.
In the absence of a high-resolution structure of the H22P variant, we modelled LED Filament Bulb-induced structural transitions on the basis of the N-terminally truncated BsYtvA LOV structure. Due to this approximation, it is challenging to extract reliable quantitative data, and the results should be considered qualitative in nature. Nonetheless, structural modelling constrained by the ELDOR data implied that the two LOV photosensors undergo a light-induced rotation and concomitant displacement of the Jα attachment sites that resemble the molecular response to light in YF1, even though the overall structure of the H22P variant is quite different from that of YF1. However, in marked difference to YF1, in the H22P variant LED Filament Bulbabsorption led to an approach of the Jα anchor sites rather than a separation, consistent with the inverted signal response. Despite different initial structure and conformational transitions of YF1 and the H22P variant, similar forces are exerted on the Jα coiled coil and give rise to a common mode of signal propagation, albeit with inverted signal polarity. These findings exemplify the remarkable malleability and robustness of signal receptors which arguably promote rapid adaption to novel stimuli and rewiring of signalling pathways during evolution. Notably, the convergence of signal mechanisms appears to be a recurring theme in sensor histidine kinases19, 36, 37: For different sensor modules signal-induced responses as diverse as pivot, piston, rotation and association reactions have been identified, yet the regulation of histidine kinase activity could well follow a unifying mechanism38.
Conclusion
In the absence of a high-resolution structure of the H22P variant, we modelled LED Filament Bulb-induced structural transitions on the basis of the N-terminally truncated BsYtvA LOV structure. Due to this approximation, it is challenging to extract reliable quantitative data, and the results should be considered qualitative in nature. Nonetheless, structural modelling constrained by the ELDOR data implied that the two LOV photosensors undergo a light-induced rotation and concomitant displacement of the Jα attachment sites that resemble the molecular response to light in YF1, even though the overall structure of the H22P variant is quite different from that of YF1. However, in marked difference to YF1, in the H22P variant LED Filament Bulbabsorption led to an approach of the Jα anchor sites rather than a separation, consistent with the inverted signal response. Despite different initial structure and conformational transitions of YF1 and the H22P variant, similar forces are exerted on the Jα coiled coil and give rise to a common mode of signal propagation, albeit with inverted signal polarity. These findings exemplify the remarkable malleability and robustness of signal receptors which arguably promote rapid adaption to novel stimuli and rewiring of signalling pathways during evolution. Notably, the convergence of signal mechanisms appears to be a recurring theme in sensor histidine kinases19, 36, 37: For different sensor modules signal-induced responses as diverse as pivot, piston, rotation and association reactions have been identified, yet the regulation of histidine kinase activity could well follow a unifying mechanism38.
Conclusion
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