Abstract
Bacterial flagella are cell locomotion and occasional adhesion organelles composed primarily of the polymeric protein flagellin, but to date have not been associated with any enzymatic function. Here, we report the bioinformatics-driven discovery of a class of enzymatic flagellins that assemble to form proteolytically active flagella. Originating by a metallopeptidase insertion into the central flagellin hypervariable region, this flagellin family has expanded to at least 74 bacterial species. In the pathogen, Clostridium haemolyticum, metallopeptidase-containing flagellin (which we termed flagellinolysin) is the second most abundant protein in the flagella and is localized to the extracellular flagellar surface. Purified flagellar filaments and recombinant flagellin exhibit proteolytic activity, cleaving nearly 1000 different peptides. With ~ 20,000 flagellin copies per ~ 10-μm flagella this assembles the largest proteolytic complex known. Flagellum-mediated extracellular proteolysis expands our understanding of the functional plasticity of bacterial flagella, revealing this family as enzymatic biopolymers that mediate interactions with diverse peptide substrates.
Highlights
Bacterial flagella are cell locomotion and occasional adhesion organelles composed primarily of the polymeric protein flagellin, but to date have not been associated with any enzymatic function
By computational identification of unexpected domain fusions[18], we report the discovery and experimental validation of a family of enzymatically active flagellins present in the genomes of 74 bacterial species including the pathogenic clostridia Clostridium haemolyticum, and strains of Clostridium novyi and Clostridium botulinum. We find that these flagellins harbor a catalytically active zinc-metallopeptidase domain that is localized to extracellular flagellar filaments, so resulting in flagella-embedded protease activity in structures of up to 10 μm
Sixty-one different domains were identified within the flagellin hypervariable region, revealing tremendous domain diversity associated with surface-exposed structures on the flagellar filament (Fig. 1a)
Summary
Bacterial flagella are cell locomotion and occasional adhesion organelles composed primarily of the polymeric protein flagellin, but to date have not been associated with any enzymatic function. Flagellin monomers are composed of three structural domains: slowly evolving N-terminal and C-terminal coiled-coil domains that interact in cis to form the core of the filament, and a central hypervariable region of extreme sequence variation, which forms the filament surface[8, 11] (Fig. 1a) and is largely responsible for interfacing with the environment[6] These interactions play an important role in adherence and colonization of host cells in a diverse range of mammalian[12,13,14] and nonmammalian bacterial pathogens[15, 16]. Flagellin-mediated proteolysis expands our understanding of the functional plasticity of flagellar filaments as enzymatic biopolymers, with potential for numerous roles in saprophytic bacteria and in pathogens including biofilm interactions and colonization, tissue colonization and virulence
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