{"title":"Structural and molecular dynamics simulation studies of CBL-interacting protein kinase CIPK and its complexes related to plant salinity stress.","authors":"Prabir Kumar Das, Tanya Bhatnagar, Sanhita Banik, Sambit Majumdar, Debajyoti Dutta","doi":"10.1007/s00894-024-06037-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Calcium-dependent signaling in plants is responsible for several major cellular events, including the activation of the salinity-responsive pathways. Calcium binds to calcineurin B-like protein (CBL), and the resulting CBL-Ca<sup>2+</sup> complex binds to CBL-interacting protein kinase (CIPK). The CBL-CIPK complex enhances the CIPK interaction with an upstream kinase. The upstream kinase phosphorylates CIPK that, in turn, phosphorylates membrane transporters. Phosphorylation influences transporter activity to kick-start many downstream functions, such as balancing the cytosolic Na<sup>+</sup>-to-K<sup>+</sup> ratio. The CBL-CIPK interaction is pivotal for Ca<sup>2+</sup>-dependent salinity stress signaling.</p><p><strong>Methods: </strong>Computational methods are used to model the entire Arabidopsis thaliana CIPK24 protein structure in its autoinhibited and open-activated states. Arabidopsis thaliana CIPK24-CBL4 complex is predicted based on the protein-protein docking methods. The available structural and functional data support the CIPK24 and the CIPK24-CBL4 complex models. Models are energy-minimized and subjected to molecular dynamics (MD) simulations. MD simulations for 500 ns and 300 ns enabled us to predict the importance of conserved residues of the proteins. Finally, the work is extended to predict the CIPK24-CBL4 complex with the upstream kinase GRIK2. MD simulation for 300 ns on the ternary complex structure enabled us to identify the critical CIPK24-GRIK2 interactions. Together, these data could be used to engineer the CBL-CIPK interaction network for developing salt tolerance in crops.</p>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Modeling","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s00894-024-06037-5","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Context: Calcium-dependent signaling in plants is responsible for several major cellular events, including the activation of the salinity-responsive pathways. Calcium binds to calcineurin B-like protein (CBL), and the resulting CBL-Ca2+ complex binds to CBL-interacting protein kinase (CIPK). The CBL-CIPK complex enhances the CIPK interaction with an upstream kinase. The upstream kinase phosphorylates CIPK that, in turn, phosphorylates membrane transporters. Phosphorylation influences transporter activity to kick-start many downstream functions, such as balancing the cytosolic Na+-to-K+ ratio. The CBL-CIPK interaction is pivotal for Ca2+-dependent salinity stress signaling.
Methods: Computational methods are used to model the entire Arabidopsis thaliana CIPK24 protein structure in its autoinhibited and open-activated states. Arabidopsis thaliana CIPK24-CBL4 complex is predicted based on the protein-protein docking methods. The available structural and functional data support the CIPK24 and the CIPK24-CBL4 complex models. Models are energy-minimized and subjected to molecular dynamics (MD) simulations. MD simulations for 500 ns and 300 ns enabled us to predict the importance of conserved residues of the proteins. Finally, the work is extended to predict the CIPK24-CBL4 complex with the upstream kinase GRIK2. MD simulation for 300 ns on the ternary complex structure enabled us to identify the critical CIPK24-GRIK2 interactions. Together, these data could be used to engineer the CBL-CIPK interaction network for developing salt tolerance in crops.
期刊介绍:
The Journal of Molecular Modeling focuses on "hardcore" modeling, publishing high-quality research and reports. Founded in 1995 as a purely electronic journal, it has adapted its format to include a full-color print edition, and adjusted its aims and scope fit the fast-changing field of molecular modeling, with a particular focus on three-dimensional modeling.
Today, the journal covers all aspects of molecular modeling including life science modeling; materials modeling; new methods; and computational chemistry.
Topics include computer-aided molecular design; rational drug design, de novo ligand design, receptor modeling and docking; cheminformatics, data analysis, visualization and mining; computational medicinal chemistry; homology modeling; simulation of peptides, DNA and other biopolymers; quantitative structure-activity relationships (QSAR) and ADME-modeling; modeling of biological reaction mechanisms; and combined experimental and computational studies in which calculations play a major role.