Cryo-EM structures of a bathy phytochrome histidine kinase reveal a unique light-dependent activation mechanism

Abstract

Phytochromes are photoreceptor proteins in plants, fungi and bacteria. They can adopt two photochromic states with differential biochemical responses. The structural changes transducing the signal from the chromophore to the biochemical output modules are poorly understood due to challenges in capturing structures of the dynamic, full-length protein. Here, we present the first cryo-electron microscopy structures of the phytochrome from Pseudomonas aeruginosa (PaBphP) in its resting Pfr and photoactivated Pr state. The kinase-active Pr state has an asymmetric, dimeric structure, whereas the kinase-inactive Pfr state opens up. This behaviour is different from other known phytochromes and we explain it with the unusually short connection between the photosensory and output modules. Multiple sequence alignment of this region suggests evolutionary optimisation for different modes of signal transduction in sensor proteins. The results establish a new mechanism for light-sensing by phytochrome histidine kinases and provide input for the design of optogenetic phytochrome variants.