Molecular Investigation of Periplasmic Sensor Histidine Kinase Interactions in Regulating UV Shield Formation of Cyanobacteria Nostoc Sp.

Microorganisms utilize predominant signaling systems to monitor environmental changes and modify gene expression. One of the primary adaptive mechanisms in bacteria is the Two-Component Regulatory System (TCRS), which consists of a sensor histidine kinase and a Response Regulator (RR) (Ibrahim et al., ۲۰۱۶). The histidine kinase protein detects external signals and phosphorylates the RR, which then regulates gene expression. In cyanobacteria, including Nostoc species (Janssen and Soule, ۲۰۱۶), histidine kinases are often transmembrane proteins with a sensor domain in the periplasm and a kinase domain in the cytoplasm (Affandi et al., ۲۰۱۶). This enables them to sense and react effectively to variations in the environment. Nostoc punctiforme bacteria are activated by UV stress to produce scytonemin, a protective pigment that absorbs harmful UVA radiation (Klicki et al., ۲۰۲۲). Genomic analyses suggest that the biosynthesis of scytonemin is regulated by TCRS proteins, through a signaling process likely mediated by histidine kinases (Janssen and Soule, ۲۰۱۶). However, the detailed molecular interaction between scytonemin and the sensor domain of histidine kinase has not been completely understood. This research utilizes molecular docking to explore the binding interactions between scytonemin and the periplasmic sensor domain of histidine kinase in Nostoc species. The ۳-dimensional structure of the sensor histidine kinase was obtained from UniProt (ID: A۰A۱Z۴I۲R۹), while the scytonemin structure was retrieved from PubChem database (CID: ۱۳۵۴۷۳۳۸۱). Using AutoDock Vina via Chimera software (Butt et al., ۲۰۲۰), docking simulations were conducted to generate a total of ۱۰ binding modes. The grid box used in docking was centered at coordinates x = ۱.۴۴, y = -۳.۰۲, and z = -۳.۵۶, with dimensions of ۱۱۰ Å in each direction to ensure comprehensive coverage of the binding site. The docking analysis shows that the binding energies of the conformations range from -۹.۷ to -۸.۳ kcal/mol, indicating a strong binding affinity. The optimal binding mode has an energy of -۹.۷ kcal/mol with no RMSD deviation (۰.۰۰۰) from the reference conformation. This suggests that specific interactions contribute to the stability of the scytonemin-histidine kinase complex. Important stabilizing connections involve Pi-Pi T-shaped bonds with phenylalanine units (PHE A:۳۹ and PHE A:۱۴۶) and Pi-Sigma stacking with PHE A:۱۴۹. Furthermore, Pi-Alkyl interactions with proline (PRO A:۱۳۴) and leucine (LEU A:۱۳۸) enhance the complex's hydrophobic stability. A Pi-Cation interaction between arginine (ARG A:۸۹) and an aromatic ring in scytonemin suggests an important electrostatic contribution to binding stability. These findings suggest an enduring binding process that may impact the kinase's structure and function, potentially amplifying its involvement in signal transduction. These observations provide a molecular perspective on how scytonemin contributes to the regulation of the cellular UV shield and interacts with histidine kinase to modulate bacterial stress responses under UVA radiation. This study highlights the critical role of molecular interactions that could be key to bacterial adaptation to environmental stresses. The findings hold potential for future applications in engineering UV shields at the cellular level.

کلیدواژه ها:

Nostoc bacteria ، Periplasmic sensor histidine kinase ، scytonemin ، two-component system ، molecular docking