Homology Modeling of CTR1 Protein Kinase Domain in Solanaceae Species for Identification of Salient Features in terms of Structure and Function, and Interaction Analysis with Lipids

Background: Constitutive Triple Response 1 (CTR1) is a Raf-like kinase belonging to the Mitogen-activated protein kinase kinase kinase family with central roles in cell signaling. Objective: This study was carried out in order to test if the naturally occurring plant lipids, phosphoglycerides, affect the activity of CTR1. Methods: The three-dimensional structures of the protein kinase domain of CTR1 from coffee and various species of Solanaceae, including tomato, potato, eggplant and pepper, were generated by the homology modeling technique of structure prediction using Modeller. CTR1 protein kinase sequences from the selected species were used for structure prediction in reference to the highly similar Arabidopsis CTR1 as structure template. These models were validated for their three-dimensional conformation after necessary refinements to allow the residues to fall in acceptable ranges according to the Ramachandran plot as well as the confinement of spatial arrangements as per allowed Errat and Verify3D scores. Protein-lipid molecular dockings were performed using AutoDockTools. Results: The generated models were found to possess high similarities at secondary as well as tertiary levels. Refinements and optimization of the models resulted in validated protein structures for all the homologs with scores in acceptable ranges. Docking of the AtCTR1 protein structure with phosphoglycerides produced significant interactions forming both hydrogen bonds as well as hydrophobic interactions with the active site residues of CTR1 which are also involved in various important cellular functions. Conclusion: The strong lipid-protein interactions suggest that the lipids by binding to the active site of CTR1 can affect the roles it plays in various pathways it is involved in.