Molecular model of a type III secretion system needle: Implications for host-cell sensing

Area of Science:

• Microbiology
• Structural Biology
• Bacterial Pathogenesis

Background:

• Type III secretion systems (T3SS) are critical virulence factors in Gram-negative bacteria, enabling direct injection of effector proteins into host cells.
• The T3SS comprises a basal body spanning bacterial membranes and a needle-like external structure for translocation.

Purpose of the Study:

• To determine the crystal structure of the Shigella flexneri needle subunit (MxiH).
• To build a complete model of the T3SS needle assembly using 3D electron microscopy (EM) and mutagenesis data.
• To elucidate the mechanism of host cell contact signaling and tip complex binding.

Main Methods:

• X-ray crystallography to determine the MxiH subunit structure.
• Three-dimensional (3D) electron microscopy (EM) for needle assembly reconstruction.
• Site-directed mutagenesis to investigate intersubunit interactions and signaling.

Main Results:

• The crystal structure of MxiH reveals its role as the needle subunit.
• A comprehensive model of the T3SS needle assembly was generated by integrating crystal structure and EM data.
• Mutagenesis data support a model where host cell contact signals propagate through intersubunit contacts within the needle.

Conclusions:

• The study provides atomic-level insights into the Shigella flexneri T3SS needle structure.
• The findings elucidate the mechanism of signal transduction from host cell contact to effector protein translocation.
• This work suggests a potential binding mode for the T3SS tip complex, crucial for effector delivery.