TolCs

TolCs are outer membrane channels found in many Gram-negative bacteria that function as essential components of several tripartite efflux and secretion systems. They form the outer membrane part of pumps such as AcrAB-TolC in Escherichia coli and MexAB-OprM in Pseudomonas aeruginosa, enabling the extrusion of a broad range of substrates, including antibiotics, dyes, detergents, bile salts, and toxins. TolCs also participate in certain Type I secretion systems that export proteins directly across the outer membrane.

Structurally, TolC is a homotrimer. Each subunit contributes to a 12-stranded beta-barrel that spans the outer membrane and a long periplasmic alpha-helical barrel that forms a continuous tunnel through the periplasm. The assembled TolC trimer creates a conduit through the outer membrane with its periplasmic end gated and capable of opening in response to assembly with inner membrane transporters and periplasmic adaptor proteins.

Functional efflux requires collaboration with inner membrane transporters and periplasmic adaptor proteins. The canonical tripartite pumps consist of an inner membrane transporter (often from the RND family, such as AcrB or MexB), a periplasmic adaptor protein (e.g., AcrA, MexA, MacA), and TolC. Together they translocate substrates from the cytoplasm or periplasm to the cell exterior. In secretion systems, TolC partners with inner membrane components and adaptors to export proteins like hemolysin.

TolCs contribute to intrinsic antibiotic resistance and virulence; loss or disruption of tolC increases bacterial susceptibility to numerous compounds. TolC homologs, including OprM in other species, illustrate the widespread role of this channel family in bacterial physiology.