Structural insight into toxin secretion by contact-dependent growth inhibition transporters

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Bacterial contact-dependent growth inhibition (CDI) systems are crucial for interbacterial competition.
• These systems employ type Vb secretion to deliver toxins (CdiA) via outer membrane transporters (CdiB).

Purpose of the Study:

• To determine the crystal structures of CdiB transporters from *Acinetobacter baumannii* and *Escherichia coli*.
• To elucidate the structural mechanisms underlying CdiA toxin secretion through the CdiB transporter.

Main Methods:

• X-ray crystallography
• Functional assays
• Molecular dynamics simulations

Main Results:

• CdiB transporters adopt a TpsB fold with a 16-stranded transmembrane β-barrel and two periplasmic domains.
• The pore is occluded by an N-terminal α-helix and extracellular loop 6, which exhibit conformational flexibility.
• A conserved DxxG motif on strand β1 plays a key role in regulating pore conformation and preparing for toxin ejection.

Conclusions:

• The structures provide unprecedented insight into the mechanism of CdiA toxin secretion.
• The identified DxxG motif and conformational dynamics are critical for priming the CdiB transporter pore.
• This work lays the foundation for understanding CDI system regulation and potential therapeutic targeting.