Chunnel vision. Export and efflux through bacterial channel-tunnels

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• The Escherichia coli TolC protein is crucial for exporting toxins and drugs.
• It spans the inner and outer cell membranes and the periplasmic space.
• Understanding TolC's structure is key to understanding bacterial efflux mechanisms.

Purpose of the Study:

• To describe the structural assembly of the TolC protein.
• To elucidate the functional implications of its structure for toxin and drug export.
• To highlight the conservation of this structure in Gram-negative bacteria.

Main Methods:

• Crystal structure determination of the TolC protein.
• Analysis of the protein's assembly into a trans-periplasmic cylinder and outer membrane beta-barrel.
• Comparative analysis with TolC homologues in other Gram-negative bacteria.

Main Results:

• TolC forms a unique alpha-helical trans-periplasmic cylinder (tunnel).
• This tunnel is embedded in the outer membrane via a contiguous beta-barrel (channel).
• This structure creates a large duct open to the external environment.

Conclusions:

• The TolC channel-tunnel structure is highly conserved in Gram-negative bacteria.
• This conserved structure suggests a common mechanism for TolC recruitment and opening.
• Substrate-specific inner-membrane complexes likely mediate TolC activation.