Madhavi Bhatia, NIPER Guwahati
Proteins play a very important role in various types of biological processes that occur in organisms. Protein dynamics are involved in the catalytic function of enzymes, the interaction of protein complexes or signal integration in regulatory proteins. While performing these functions the conformation state of the protein is very important. In multi-domain signalling proteins, an intricate interplay of individual domains is frequently observed, because the dynamic properties of singular domains affect the global dynamics of the system and ultimately, the biological function of the protein. One type of signalling protein recently identified is the subfamily of red-light-sensitive photoreceptors called biliverdin-linked bacteriophytochromes, that especially the group of phytochrome activated diguanylate cyclases (PadCs).
PadCs have a PAS (Period/ARNT/Single-minded)-GAF (cGMP phosphodiesterase/adenylate cyclase/FhIA)-PHY (phytochrome-specific) design of the photosensory module (PSM) and a GGDEF output domain. The GAF domain provides the co-factor (biliverdin) binding pocket and the PHY domain stabilizes the light state through the tongue element. The N-terminal segment with cysteine residues covalently binds the chromophore to the protein. The segment also interacts with the tongue and residues of the co-factor binding site in the Pr state. These three functional elements were involved in light sensing and signal transduction, after the structural rearrangements following the isomerization of biliverdin. It is found that the PAS-GAF core acts as a key player which influences the absorption properties of individual PadCs in their Pr states.
Red-light-induced regulation of enzyme activity is affected by the linker length present in the enzyme. The function of linker length depends on the presence and composition of coiled-coil heptad repeats. Mostly the linker length present differs by multiples of 7 residues. The sensor and effector are joined by this characteristic coiled-coil linker. Preliminary spectral and enzymatic analysis of the family members of PadCs showed that homologs with linker lengths not equal to multiples of seven/heptad repeats inhibit the upregulation of DGC activity upon cofactor isomerization.
An asymmetric light state of the enzyme is potentially advantageous for switching between inhibiting and stimulating coiled-coil registers but is not a prerequisite for red-light-induced upregulation of DGC activity. Asymmetry cannot be assigned to any specific structural element but the exchange of a single domain or feature can cause deactivation or restoration of symmetry of the enzyme. PHY domain comprises 2 helices- GAF domain and coiled-coil linker. These are part of the phytochrome-spanning helical spine and form an essential part of the characteristic 4 helix bundle (Quasi) dimer interface observed in many GAF models. This dimer binds to one GTP molecule per promoter, requiring GGDEF domains to occupy positions advantageous for intermediate (pppGpG) and eventually product (c-di-GMP) formation at the interface. The PHY-tongue plays a crucial role in signal integration. If both PHY interface and linker correspond to the IsPadC sequence, upregulation of enzymes occurs. However, if the PHY interface comes from MpPadC, no upregulation of DGC turnover is observed. Thus, the PHY domain plays a central role in mediating signal integration in phytochrome-regulated DGCs by proper communication between sensor and effector. The direct connection to the coiled-coil linker enables signal integration and modulation of the dynamic range.
PadCs are highly complex systems with their biochemical function and enzymatic behaviour occurring by an intricate interplay of various domains and structural features. Photoactivation in bacteriophytochrome is controlled by a dynamic equilibrium of all essential modules and structural elements ranging from chromophore surrounding to the output module. The structural asymmetry of the light-activated state is potentially advantageous but is not absolutely necessary for the regulation of enzymatic activity in PadCs. Communication between the photosensory module and the GGDEF effector plays an essential role in signal transduction, with the PHY domain dimer interface bridging these 2 components.
Thus, there are various intricate processes that occur during light signal integration and transduction in the photosensory system.
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Source:-Cornelia B, Nikolina T, Marco B, Geoffrey G, Andreas W. The PHY domain dimer interface of bacteriophytochromes mediates cross-talk between photosensory modules and output domains. Journal of molecular biology. 2021 Jun 9. https://doi.org/10.1016/j.jmb.2021.167092.
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