Structural insights into outer membrane protein biogenesis in pathogenic Neisseria

Area of Science:

• Microbiology
• Structural Biology
• Molecular Biology

Background:

• Neisseria gonorrhoeae (Ngo) causes gonorrhea, a prevalent sexually transmitted infection with significant public health implications, including increased HIV risk, infertility, and blindness.
• The biogenesis of essential outer membrane proteins (OMPs) in Ngo relies on the β-barrel assembly machinery (BAM).

Purpose of the Study:

• To determine the cryoelectron microscopy (cryo-EM) structure of the Ngo β-barrel assembly machinery (NgBAM).
• To elucidate the mechanism of OMP biogenesis in Ngo and identify potential therapeutic targets.

Main Methods:

• Cryoelectron microscopy (cryo-EM) was employed to obtain the high-resolution structure of NgBAM.
• Molecular dynamics (MD) simulations were utilized to investigate the dynamic behavior and interactions within NgBAM.

Main Results:

• The cryo-EM structure revealed NgBAM in an inward-open state, with unique features in its barrel seam (partial pairing of strand β1 with β16).
• Polypeptide transport-associated (POTRA) domains showed characteristics similar to the outward-open state of E. coli BAM.
• MD simulations highlighted distinct dynamics and interplay between NgBamA and NgBamD POTRA domains.
• No outward-open state of NgBAM was observed.

Conclusions:

• The findings propose a novel mechanism for OMP recognition and insertion in Ngo, initiated in the inward-open state.
• Understanding NgBAM structure and dynamics provides a foundation for developing targeted interventions against gonorrhea.