Asymmetric activation mechanism of a homodimeric red light-regulated photoreceptor

Abstract

Organisms adapt to environmental cues using diverse signaling networks. In order to sense and integrate light for regulating various biological functions, photoreceptor proteins have evolved in a modular way. This modularity is targeted in the development of optogenetic tools enabling the control of cellular events with high spatiotemporal precision. However, the limited understanding of signaling mechanisms impedes the rational design of innovative photoreceptor-effector couples. Here, we reveal molecular details of signal transduction in phytochrome-regulated diguanylyl cyclases. Asymmetric structural changes of the full-length homodimer result in a functional heterodimer featuring two different photoactivation states. Structural changes around the cofactors result in a quasi-translational rearrangement of the distant coiled-coil sensor-effector linker. Eventually, this regulates enzymatic activity by modulating the dimer interface of the output domains. Considering the importance of phytochrome heterodimerization in plant signaling, our mechanistic details of asymmetric photoactivation in a bacterial system reveal novel aspects of the evolutionary adaptation of phytochromes.

Instability in a coiled‐coil signaling helix is conserved for signal transduction in soluble guanylyl cyclase

“…Coiled‐coil helices are increasingly implicated in signal transduction and for this reason are sometimes referred to as signaling helices . Examples include the bacterial two‐component sensor histidine kinase YF1, which undergoes a change in coiled‐coil helix cross‐over angle upon activation, transcriptional regulator DhaR, which undergoes a rotation of coiled‐coil helices during activation, and both Nek2 kinase and phytochrome‐regulated diguanylyl cyclase, which have been suggested to undergo a shift in coiled‐coil register during signal transduction …”

Signal transduction in photoreceptor histidine kinases

“…As the PCMs have mostly been structurally elucidated as truncated proteins without attached effector modules, the observed quaternary structure need not necessarily correspond to the one in the full‐length receptor. The parallel arrangement appears physiologically more relevant as it is supported by structural data on BPhys with attached effector modules and by the parallel homodimeric nature of the most common BPhy effector modules, see above. Notably, the architecture of the parallel PCM homodimer is reminiscent of the LOV‐SHK architecture that also features parallel homodimers, α‐helical interface and laterally suspended globular sensor domains of the PAS superfamily.…”

“…With but few exceptions, the PCMs have been structurally elucidated in isolation, that is, as PAS‐GAF‐PHY constructs without covalently attached C‐terminal effector module. Where present in the structure, the effectors are mostly connected to the PCM via a continuous parallel coiled coil, thus possibly restricting the quaternary structures the PCM can adopt in the Pr and Pfr states. In particular, it remains to be seen whether the large‐scale splaying apart of the PHY domains observed for the isolated Dr BPhy PCM manifests to the same extent within the context of full‐length native and engineered BPhy receptors .…”

“…In particular, it remains to be seen whether the large‐scale splaying apart of the PHY domains observed for the isolated Dr BPhy PCM manifests to the same extent within the context of full‐length native and engineered BPhy receptors . In fact, recent structures of a BPhy‐GGDEF enzyme indicate that the conformational transitions within the context of a full‐length receptor are of much smaller amplitude . Regardless, the long continuous α helices are conducive to downstream relay of the conformational signal, see below.…”

Light‐induced complex formation of bacteriophytochrome RpBphP1 and gene repressor RpPpsR2 probed by SAXS

“…Yet another full‐length BphP structure is type 5 Is PadC from Idiomarina sp. This BphP allows red‐light regulation of the second messenger bis ‐(3′‐5′)‐cyclic dimeric guanosine monophosphate (c‐di‐GMP) by diguanylyl cyclase activity in the C terminus GGDEF domain . Despite the differences at the C terminus, all BphP types share common light‐induced structural elements that transmit conformation changes to their C‐terminal domains through a long helix (hI).…”