Basic Leucine Zippers: Aureochromes Versus the Rest

Abstract

AbstractThe 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.