Basic Leucine Zippers: Aureochromes Versus the Rest

Abstract

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.

Identification of promoter targets by Aureochrome 1a in the diatom Phaeodactylum tricornutum

“…As it is postulated that AUREOs evolved from a non-light-sensitive form to a light-sensitive form ( Khamaru et al , 2022a , Preprint), gene regulation of PtAUREO1a in the absence of BL illumination (RL or dark) might be indicative of its ancestry, and PtAUREO1a may have further evolved to serve comprehensive roles utilizing the sensory domain. Indeed, several studies have confirmed that the conformational changes of PtAUREO1a are influenced by BL illumination, specifically due to the changes in structure of the LOV domain ( Herman et al , 2013 ; Banerjee et al , 2016b ; Heintz and Schlichting, 2016 ; Goett-Zink et al , 2023 ).…”

Assessing Combinatorial Diversity of Aureochrome Basic Leucine Zippers through Genome-Wide Screening

“…This is due to relatively low interface area and poor graph-theoretic and information-theoretic parameters. Interestingly, the aureochrome-2 from all photosynthetic algae forms a distinct clade from the remaining aureochrome subtypes [Khamaru et al, 2022], and aureochrome-2 from Vaucheria frigida possesses a non-functional LOV sensor [Takahashi et al, 2007]. Another interesting case is model_37.…”

Assessing combinatorial diversity of aureochrome bZIPs through genome-wide screening

“…And, it is still expanding with the gene duplication of the different bZIP sequences. Aureochromes are considered to be a rare amalgamation of a photoreceptor and a TF, with bZIPs as an effector (Khamaru et al, 2022). A sensory TF like aureochrome can activate the global TF interaction network not only by interacting with the DNA but also by finding compatible monomeric bZIP partners.…”