Type VI secretion and bacteriophage tail tubes share a common assembly pathway

Area of Science:

• Microbiology
• Molecular Biology
• Structural Biology

Background:

• The Type VI secretion system (T6SS) is a critical nanomachine for bacterial intercellular interactions, delivering effector proteins to target cells.
• Current models depict T6SS as an inverted phage tail, with Hcp proteins forming a central tube and TssB/C forming an outer sheath.

Purpose of the Study:

• To investigate the in vivo assembly of the Hcp tube within the T6SS.
• To elucidate the role of Hcp-Hcp interactions and TssB in T6SS structure formation.
• To compare T6SS assembly with bacteriophage tail assembly mechanisms.

Main Methods:

• Utilized a cysteine substitution approach to probe Hcp protein interactions and assembly.
• Investigated the interaction between Hcp and TssB, a sheath component.
• Analyzed the role of VgrG in the assembly of the Hcp tubular structure.

Main Results:

• Demonstrated that Hcp hexamers assemble into ordered, head-to-tail stacked tubes in vivo.
• Showed that these Hcp tubes serve as a scaffold for the polymerization of the TssB/C sheath.
• Identified VgrG, but not TssB/C, as a key regulator of Hcp tubular structure assembly.

Conclusions:

• The Hcp protein forms a structurally ordered tube essential for T6SS assembly.
• T6SS assembly shares conserved mechanisms with bacteriophage tail assembly, particularly in tube formation.
• This study provides new insights into the structural organization and assembly dynamics of the T6SS.