Structure of the type VI secretion system contractile sheath

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• The type VI secretion system (T6SS) is a complex nanomachine used by bacteria for inter-cellular transport.
• T6SS mediates contact-dependent delivery of effector proteins into target cells, influencing microbial communities and host interactions.
• Understanding the structural basis of T6SS contraction is crucial for deciphering its mechanism of action.

Purpose of the Study:

• To determine the atomic-resolution structure of a contracted Vibrio cholerae T6SS sheath.
• To elucidate the molecular mechanisms underlying T6SS sheath assembly and contraction.
• To investigate the interaction between the T6SS sheath and the accessory ATPase ClpV.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to obtain an atomic-resolution structure of the contracted T6SS sheath.
• Bioinformatic analysis and structural comparisons were employed to understand subunit interactions and conserved folds.
• Biochemical assays were utilized to study the role of ClpV in sheath dynamics.

Main Results:

• The contracted Vibrio cholerae T6SS sheath is composed of VipA and VipB proteins forming a six-start helix.
• A conserved core domain, assembled from β strands of VipA and VipB, stabilizes the helical structure.
• The distinct outer layer structure suggests a mechanism for interaction with the ClpV ATPase, facilitating repeated cycles of effector delivery.

Conclusions:

• The study provides the first atomic-resolution structure of a contracted T6SS sheath, revealing conserved and distinct features compared to phage sheaths.
• The findings offer mechanistic insights into the assembly and function of contractile bacterial nanomachines.
• This work lays the foundation for understanding how T6SS facilitates macromolecule translocation across membranes.