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Extracellular transfer of a conserved polymerization factor for multi-flagellin filament assembly in Caulobacter

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SUMMARY:

Unidirectional growth of filamentous protein assemblies including the bacterial flagellum relies on dedicated polymerization factors (PFs). The molecular determinants and structural transitions imposed by PFs on multi-subunit assembly are poorly understood. In this study, published in Cell Reports by GCIR member Prof. Patrick Viollier and team member Dr. Nicolas Kint, the authors unveil FlaY from the polarized α-proteobacterium Caulobacter crescentus as a defining member of an alternative class of specialized flagellin PFs. Unlike the paradigmatic FliD capping protein, FlaY relies on a funnel-like β-propeller fold for flagellin polymerization. FlaY binds flagellin and is secreted by the flagellar secretion apparatus, yet it can also promote flagellin polymerization exogenously when donated from flagellin-deficient cells, serving as a transferable, extracellular public good. While the surge in FlaY abundance precedes bulk flagellin synthesis, FlaY-independent filament assembly is enhanced by mutation of a conserved region in multiple flagellin paralogs. The authors suggest that FlaYs are (multi-)flagellin PFs that evolved convergently to FliDs yet appropriated the versatile β-propeller fold implicated in human diseases for chaperone-assisted filament assembly.

Full article: https://doi.org/10.1016/j.celrep.2023.112890

This work has been funded by Swiss National Science Foundation (SNSF), UNITEC, and Swiss Life Foundation Jubiläumsstiftung.

Why is it important?

The flagellum organelle is a complex multi-protein assembly best known for its role in bacterial rotational propulsion. However, it also plays roles in infection, including adhesion and immune modulation, for example in pathogenic Gram-negative bacteria such as Salmonella enterica, Campylobacter jejuni, Helicobacter pylori or Pseudomonas aeruginosa. While flagella-mediated adhesion is important in host colonisation, shed flagellar filament subunits (flagellin) are detected by the innate immune receptor TLR5. Maintaining the flagellum in an assembled state is therefore important for motility and adhesion of bacteria, but also to minimize detection by host surveillance systems. Therefore, the study of the nature and functions of bacterial flagella is extremely important to treat and prevent infections, potentially by vaccine development.

Here, the authors identify an alternative flagellin polymerisation factor, FlaY, that promotes the assembly of multi flagellin filaments in the bacterial model Caulobacter crescentus and related Gram-negative bacteria. The authors suggest that FlaY promotes filament polymerization by tip extension, like a bricklayer building a chimney. Like these bricks, flagellin subunits are channelled through the growing chimney and added to the tip by FlaY. Remarkably, the authors found that the chimney builder FlaY can be shared by different chimneys: it can be donated from neighbouring cells to build the flagellum in cells that lack FlaY. Flagellin can also be genetically engineered to assemble a flagellum without FlaY, but this flagellum is short and poorly functional. Therefore, FlaY is needed for efficient flagellum construction in C. crescentus.

 

10 Aug 2023

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