PD-T4-9
Description
The CmdTAC system operates through a hierarchy of components where roles are distinctly defined:
- Effector: The CmdT protein (formerly PD-T4-9-A) is the Toxin. Its functional type is Enzymatic, specifically an ADP-ribosyltransferase (ART). It performs the irreversible defense action by chemically modifying the target.
- Sensor: The CmdC protein (formerly PD-T4-9-C) is the Chaperone. Its functional type is Binding/Structural. It maintains the inactive state and serves as the molecular surveillance unit that recognizes the infection.
- Inhibitor/Switch: The CmdA protein (formerly PD-T4-9-B) is the Antitoxin. Its functional type is Regulatory/Substrate. It neutralizes the Toxin (CmdT) and its controlled degradation is the essential switch mechanism for activation. The Activator/Trigger is an external Viral Structural Protein, such as the Gp23 capsid protein of T4 phage.
The CmdTAC system is encoded within a tri-cistronic operon, meaning the three component genes are transcribed together. This organization is crucial for the precise co-translational assembly and regulation of the complex. While the system is often found within prophages (integrated viral genomes) in E. coli, the functional genes are arranged in a specific order:
- The gene for the Chaperone (CmdC) often initiates the operon.
- The Antitoxin gene (CmdA) typically follows, preceding the Toxin.
- The Toxin gene (CmdT) is usually the downstream component.
Moleular mechanism
The chaperone CmdC normally promotes neutralization of CmdT by CmdA. During infection by T4 phage, the major capside protein (gp23) outcompetes the antitoxin CmdA to bind to the chaperone CmdC. CmdC disassociates from CmdT and CmdA complex and interacts with the phage capsid protein instead. In the absence of the SecB-like chaperone, the antitoxin is prone to aggregation and proteolytic degradation by the ClpP protease thereby freeing the toxin. The toxin CmdT itself is an ADP-ribosyltransferase that primarily modifies the N6 position of adenine in GA dinucleotides found in mRNAs. Notably, GA nucleotides are almost always found within the Shine-Dalgarno sequences of bacterial (AGGAGG) and T4 (GAGG) transcripts. ADP-ribosylation of Shine-Dalgarno sequences may prevent modified transcripts from engaging ribosomes and initiating translation. Also, the modification of GA dinucleotides within an mRNA may disrupt base-pairing with tRNAs or may stall ribosomal translocation. This modification blocks the translation of mRNAs and the cessation of creating new proteins aborts the infection, preventing the phage from spreading beyond the host to infect other bacteria.
Example of genomic structure
The PD-T4-9 is composed of 3 proteins: PD-T4-9_A, PD-T4-9_B and PD-T4-9_C.
Here is an example found in the RefSeq database:
The PD-T4-9 system in Vibrio parahaemolyticus (GCF_001700835.1, NZ_CP010883) is composed of 3 proteins PD-T4-9_C (WP_065870458.1) PD-T4-9_B (WP_141106056.1) PD-T4-9_A (WP_065870460.1)