The Impact of Toxic Effector Molecule TagX on the Amino Acid Conformation of the Hcp1 Monohexameric Ring in Acinetobacter baumannii Type VI Secretion System Utilizing Bioinformatics Tools and an AI System

Limited information is currently available regarding the contraction mechanism of the Hcp-1 hemolysin-coregulated protein within the type VI secretion system (T6SS) of Acinetobacter baumannii, particularly about the secretion of toxic effectors. This research aimed to evaluate the mechanism underlying the contraction of the Hcp1 nanotube in response to the putative toxic effector TagX protein by employing bioinformatics tools and the artificial intelligence (AI) DeepMind system. To achieve this goal, the amino acid sequence of Hcp1 from A. baumannii was retrieved from the GenBank database under accession no. WP_000653195.1 and its three-dimensional (3D) structure as a whole tail and monomer was generated utilizing the AlphaFold2 AI from DeepMind. The 3D structure of the TagX hydrolase from A. baylyi ADP1 was predicted by the ExPASy auto-modeling software (ExPASy). The prepared TagX ligand was subsequently docked to the target site of selected amino acids within the Hcp1 nanotube via AutoDock Vina in the Schrödinger platform. The conformational changes of the amino acid side chains upon docking were examined using RoseTTAFold, and side chain rotational angles (Ψ/Φ) were detected based on the Dunbrack rotamer package. The molecular docking indicated that TagX toxin binds to His108, Arg98, Ser78, and Glu121 within the Hcp1 nanotube by H-bond. This interaction induces a rotameric shift in the dihedral angles of the aforementioned amino acids, initiating the contraction of the Hcp1 tail/tube via VgrG1 (gp27) contractile sheath and ClpV ATPase. This resulted in the propulsion of the effector molecule through Hcp1 to the tip of the T6SS complex and subsequent injection into prey cells.