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All of the secretion systems discussed above use some sort of structure formed of β-sheets assembled into a ring called a β-barrel to get them through the outer membrane. Some of these β-barrels are part of the secretion apparatus itself, while others, like TolC, are recruited from other functions in the cell. However, in type V systems, secreted proteins carry their own β-barrel with them in the form of a domain of the protein that can create a β-barrel when it gets to the outer membrane. These proteins are called autotransporters because they transport themselves.

The mechanism used by autotransporters is illustrated in Figure 2.40, which also shows their basic structure. Most autotransporters consist of four domains, the translocator domain at the C terminus that forms a β-barrel in the outer membrane, an adjacent flexible linker domain (not shown) that may extend into the periplasm, a passenger domain that contains the functional part of the autotransported protein, and sometimes a protease domain that may cleave the passenger domain off the translocator domain after it passes through the channel formed by the translocator domain.

Figure 2.40 Structure and function of a typical autotransporter. A Haemophilus influenzae adhesin is shown; the length in amino acids of each domain, where known, is indicated by the number above the structure, as are some of the important amino acids in the protease domain. The transporter domain at the C terminus that forms a β-barrel in the outer membrane is shown in orange; the passenger domain and the protease domain that cleaves the passenger domain off the transporter domain outside the cell are shown in purple. The flexible linker domain is not indicated. The signal sequence that is cleaved off when the protein passes through the SecYEG (Sec) channel in the inner membrane is shown in black. OM, outer membrane; IM, inner membrane. Modified from Surana NK, Cotter SE, Yeo H-J, et al, in Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis (ASM Press, Washington, DC, 2005).

Autotransporters are typically transported through the inner membrane using the SecYEG channel, so they have a signal sequence that is cleaved off as they pass into the periplasm. Their translocator domain then enters the outer membrane, where it forms a 12-stranded β-barrel. This assembly does not occur by itself but requires the same accessory factors used for the assembly of many secretins, including the periplasmic chaperone, Skp, and the Bam complex (see above). The flexible linker domain guides the passenger domain into and through the channel to the outside of the cell. The passenger domain can then be cleaved off by its own protease domain or remain attached to the translocator domain and protrude outside the cell, depending on the function of the passenger domain. The source of the energy for autotransportation is unclear, since, as mentioned, there is no ATP or GTP in the periplasm and the outer membrane does not have a membrane potential. One possibility is that the autotransporter arrives at the periplasm in a “cocked” or high-energy state that drives its own transport.

The prototypical autotransporter is the immunoglobulin A protease of Neisseria gonorrhoeae. It is involved in evading the host immune system by cleaving IgA antibodies on mucosal surfaces. Most known autotransporters are large virulence proteins that perform various roles in bacterial pathogenesis or in helping to evade the host immune system. The IcsA protein of Shigella flexneri, a cause of bacterial dysentery, is localized to the outer membrane, where it recruits a host actin-regulating protein, which in turn recruits another host complex that polymerizes host actin into filaments, pushing the bacterium through the eukaryotic cell cytoplasm as part of the infection mechanism, a process called actin-based motility.