Team:Slovenia/Background/Flagellin

From 2008.igem.org

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Flagellin



Many bacteria are motile due to the propelling ability of their flagella. A flagellum consists of the Mot complex, which is a remarkable »nanoengine« that rotates the filament of the flagellum. The filament is a polymer of monomeric units, called flagellin. Flagellin is a protein consisting of a conserved inner core, accountable for the self-assembly of monomeric units, and an outer surface portion, which substantially varies among bacterial species. Due to the assembly of 11 flagellin monomers in one turn, filament acquires its helical shape. Flagellin consists of four linearly connected domains which fold as coiled coils and are labeled D0, D1, D2 and D3 where the D0 domains of flagellins form the most inner portion of the cylindrical filament and D3 the most outer, surface portion. The N-terminal chain starts from D0, going through D1, D2 and reaches D3, and then comes back through D2 and D1, and the C-terminal chain ends in D0.

Tertiary structure of flagellin of enteric bacteria and their assembly into the filament mediated by D0 and D1 coiled-coil segments.

Functionality of flagella is essential for the virulence of many bacteria and therefore represents an appropriate recognition signal for the innate immune system. It is also very appropriate that the cellular receptors recognize the most conserved segment of flagellin, which is essential for the assembly of functional flagella.
Flagellin of most bacteria is recognized by the Toll-like receptor 5 (TLR5), which is localized on cell membrane and recent unpublished results indicate that murine TLR11 also recognizes it. TLR5 is localized on the membrane of epithelial cells and cells of the immune system (immature DC, monocytes, NK, T-cells). It has been demonstrated that the N- and C-terminal conserved segments, consisting of 100-200 residues of flagellin are required for the recognition by TLR5, while the central segment, which is more immunogenic does not have a role in the activation of innate immune response, only as an antigen for adaptive immune response.

Ribbon structure of the molecular model of FliC flagellin of E.coli with indicated N- (green) and C-terminal (red) segments that are required for TLR5 activation.


Some bacteria have developed flagellins that avoid this recognition, yet they still have a functional flagella. So how do they manage to escape the immune recognition unpunished, that is with functional flagella? Recent crystal structure (Galkin et al, 2008) provided this answer, by demonstrating that these types of bacteria assemble flagellar filaments out of 7 rather than the usual 11 molecules of flagellin per helical turn.