همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

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

نویسندگان :

Maryam Eskafi¹ Maryam Azimzadeh Irani²

1- دانشگاه شهید بهشتی 2- دانشگاه شهید بهشتی

کلمات کلیدی :

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

چکیده :

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., 2016). The histidine kinase protein detects external signals and phosphorylates the RR, which then regulates gene expression. In cyanobacteria, including Nostoc species (Janssen and Soule, 2016), histidine kinases are often transmembrane proteins with a sensor domain in the periplasm and a kinase domain in the cytoplasm (Affandi et al., 2016). This enables them to sense and react effectively to variations in the environment. Nostoc punctiform bacterias are activated by UV stress to produce scytonemin, a protective pigment that absorbs harmful UV-A radiation (Klicki et al., 2022). 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, 2016). 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 3-dimensional structure of the sensor histidine kinase was obtained from UniProt (ID: A0A1Z4I2R9), while the scytonemin structure was retrieved from PubChem database (CID: 135473381) information source. Using AutoDock Vina via Chimera software (Butt et al., 2020), docking simulations were conducted to generate a total of 10 binding modes. The grid box used in docking was centered at coordinates x = 1.44, y = -3.02, and z = -3.56, with dimensions of 110 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 -9.7 to -8.3 kcal/mol, indicating a strong binding affinity. The optimal binding mode has an energy of -9.7 kcal/mol with no RMSD deviation (0.000) 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:39 and PHE A:146) and Pi-Sigma stacking with PHE A:149. Furthermore, Pi-Alkyl interactions with proline (PRO A:134) and leucine (LEU A:138) enhance the complex’s hydrophobic stability. A Pi-Cation interaction between arginine (ARG A:89) 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.