Aureochromes are unique blue light-responsive LOV (Light Oxygen Voltage) photoreceptors cum basic leucine zipper (bZIP) transcription factors (TFs), present exclusively in photosynthetic marine stramenopiles. Considering the availability of the complete genome sequence, this study focuses on aureochromes from Ectocarpus siliculosus. Aureochromes mediate light-regulated developmental responses in this brown photosynthetic algae. Both the LOV sensor and the bZIP effector shows overall sequence-structure conservation. The structurally similar LOV+bZIP modules of aureochrome homologs/paralogs prefer a dimeric state. Besides a heterogeneous linker connecting the sensor-effector and a flexible N-terminal region, the sequence composition of both domains is vital. Aureochromes execute diverse cellular responses in different photosynthetic stramenopiles – though their activities can vary even within a given algal species. Therefore, it is important to understand whether aureochromes select dimerization partners from the same family or interact with other bZIPs as well. To regulate multifarious biological activities, it is possible that aureochromes activate the global TF interaction network. Following homo/heterodimer modeling, we address the compatibility of dimerization partners by screening through heptad repeats. We evaluate the dimer interface area in terms of gain in solvation energy and the number of hydrogen bonds/salt bridge interactions. We further explore the relative stability of these structures from a graph-theoretic perspective through well-studied measures such as the energy of the graph, average participation coefficient, and betweenness centrality. Furthermore, we also conduct an information-theoretic analysis using hitherto understudied measures such as network information centrality and Kullback-Leibler divergence. We find that all our investigations into the relative stability of the dimers using diverse methods from bioinformatics, network science, and, information theory are in harmonious agreement. Coupling preferences of monomers in aureochromes can be further translated to design novel optogenetic tools useful for understanding human development and disease.

The photoreceptor cum transcription factors, Aureochromes, is present exclusively in marine photosynthetic algae. Co-existence of Light-Oxygen-Voltage (LOV) sensor and basic leucine zipper (bZIP) effector in aureochromes is unique -- no other photoreceptors barring aureochromes are known to possess bZIP as effector. The ability of aureochromes to participate in diverse biological activities, inverse topological arrangement make them a model protein not only to study light-dependent gene expression or transcriptional regulation but also as potential optogenetic scaffold. While detailed structural information is available for the LOV sensor, 3D structural information is absent for bZIP/bZIP+linker+LOV module. This study therefore aims for a thorough investigation of the bZIP domains from aureochromes and others, and their interaction with substrate DNA using tools from sequence/structural bioinformatics and network theory. With an in-depth comparison between 26 aureochrome subtypes and 147 plant/ophistokont bZIPs, we explore important residues at basic region and zipper - necessary for dimerization stability and DNA binding specificity. Perhaps the most notable finding is the unique histidine substitution at the DNA binding signature sequence of aureochromes, completely absent in any other bZIPs. Not only is this residue important for DNA binding, this can serve as a potential switch point in aureochrome/bZIP evolution. An all-atom network analysis on representative bZIP-DNA co-crystal structures, especially the measurement of eigenvector centrality, further adds importance to hydrophobic interactions in the zipper region to stabilize bZIP dimer and facilitate DNA binding.

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Aureochromes are unique blue light-responsive LOV (Light Oxygen Voltage) photoreceptors cum basic leucine zipper (bZIP) transcription factors (TFs), present exclusively in photosynthetic marine stramenopiles. Considering the availability of the complete genome sequence, this study focuses particularly on aureochromes from Ectocaupus siliculosus. Aureochromes mediate light-regulated developmental responses in this brown photosynthetic algae. Both the LOV sensor and the bZIP effector shows sequence-structure conservation. The LOV+bZIP modules of aureochrome homologs/paralogs are not only structurally similar but also show an identical oligomeric state -- preferably dimeric. Aureochromes execute diverse cellular responses in different photosynthetic stramenopiles -- though their activities can vary even within a given algal species. Besides a heterogeneous linker connecting the sensor-effector and a flexible N-terminal region, the sequence composition of both the domains is vital. Therefore, it is important to understand whether aureochromes select dimerization partners from the same family or interact with other bZIPs as well. To regulate multifarious biological activities, it is possible that aureochromes activate the global TF interaction network. Following homo/heterodimer modeling, we address the compatibility of dimerization partners by screening through heptad repeats. We evaluate the dimer interface area in terms of gain in solvation energy as well as the number of hydrogen bonds/salt bridge interactions. We further explore the relative stability of these structures from a graph-theoretic perspective through well-studied measures such as the energy of the graph and average participation coefficient. Furthermore, we also conduct an information-theoretic analysis using network information centrality and Kullback-Leibler divergence. We find that all our investigations into the relative stability of these dimers using diverse methods from bioinformatics, network science, and, information theory are in harmonious agreement. Our approach and findings should facilitate the design of experiments.