Structural insights into the assembly of the type III secretion needle complex

Area of Science:

• Microbiology and Molecular Biology
• Structural Biology
• Bacterial Pathogenesis

Background:

• Type III secretion systems (TTSSs) are crucial virulence factors in many bacterial pathogens, enabling direct translocation of effector proteins into host cells.
• Understanding the structural dynamics of TTSS components is essential for deciphering the mechanism of protein secretion and developing targeted interventions.

Purpose of the Study:

• To determine the high-resolution structures of the Salmonella typhimurium needle complex and its assembly precursor, the bacterial envelope-anchored base.
• To investigate the structural changes and protein dynamics during needle complex assembly and their implications for TTSS function.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to resolve the structures of the needle complex and base at 17-angstrom resolution.
• In vivo oligomeric states of the base and needle complex were analyzed.
• The role of the protein PrgJ during needle assembly was examined.

Main Results:

• The study revealed the structures of the Salmonella typhimurium needle complex and its assembly precursor, the base.
• Both structures were observed in multiple oligomeric states in vivo.
• Needle assembly involved the recruitment of PrgJ and significant conformational changes, forming scaffolds for PrgJ and the needle substructure.

Conclusions:

• The conformational changes during needle assembly provide a structural basis for anchoring key components and may facilitate substrate-specificity switching in TTSS.
• These findings offer critical insights into the assembly mechanism and functional regulation of type III secretion systems.