Phosphorylation-Dependent Conformational Ensemble Study of BRI1-BR-BAK1 Complex in BR Signalling

Abstract

Phosphorylation is a central post-translational modification that governs various signal transduction pathways. This process is dynamically controlled by protein kinases and protein phosphatases, allowing for reversible modifications. Kinase-facilitated protein phosphorylation significantly contributes to diverse plant functions encompassing abiotic stress reactions, immune responses, developmental pathways, and metabolic regulation. Phytohormones are critical chemical messengers which regulate plant homeostasis and metabolic pathways. Brassinosteroids (BRs) are essential phytohormones which are involved in the development of plants through Brassinosteroid signaling pathway and transduce their signals by protein phosphorylation. Oryza sativa (O. sativa) is a staple food for over half of the world's population. BR signaling in O. sativa is crucial for a wide range of developmental processes and stress responses. By modulating growth, reproduction, stress tolerance, and interaction with other hormonal pathways, BRs contribute to the overall performance and adaptability of O. sativa plants in their environment. While studies in Arabidopsis have contributed to a deeper understanding of the BR signaling pathway, the knowledge of BR signaling in O. sativa, a representative monocot model plant, remains elusive. This study addresses the limited knowledge of BR signaling in O. sativa by evaluating the phosphorylation-mediated binding patterns of a key receptor complex known as Brassinosteroid Receptor Kinase and BRI1-Associated Kinase 1 complex in BR signaling to investigate the impact of phosphorylation. By utilizing molecular docking approach, we characterized the interaction modes between phosphorylated and unphosphorylated complexes. These findings revealed a more stable binding in the phosphorylated complexes. Next, molecular dynamics simulation analysis unraveled distinct conformational changes in phosphorylated versus unphosphorylated BRI1 and assisted in the exploration of pivotal role of phosphorylation in structure-function paradigm. Notably, phosphorylation introduced significant variations in the secondary structure elements due to the structural adaptations. This exploration may contribute to our understanding of the intricate regulatory mechanisms underlying BR signaling. In the broader context of O. sativa metabolism, our study contributes to unraveling the complex interplay of conformational changes in receptor kinases and providing a foundation for future research in monocot plants. Overall, this Phosphorylation-Dependent Conformational Ensemble Study of BRI1-BR-BAK1 Complex in BR Signalling viii Abstract investigation advances our comprehension of BR signaling in O. sativa by highlighting the significance of phosphorylation-driven conformational changes in modulating plant growth and developmental pathways. These findings may provide valuable insights for designing better therapeutic interventions that may target the BR signaling pathway for agricultural or biomedical purposes. By achieving a more profound comprehension of BR signaling pathways, this knowledge may facilitate in obtaining better crop yield with enhanced productivity and stress resistance.