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Caulton, S. G.

Publications and source records attributed to Caulton, S. G..

4 recordsLinked to original sources

A C-terminal Processing Protease Implicated in Flagellin Turnover and Developmental Progression in a Bacterial Predator

Carboxy-terminal processing proteases (CTPs) are widely conserved bacterial proteases implicated in protein maturation, quality control, and stress responses, yet many family members functions remain unclear. Here, we characterise Bd0967, a previously unstudied CTP from the predatory bacterium Bdellovibrio bacteriovorus, and its role in flagellar function during predatory development. Crystal structures reveal a self-compartmentalised protease in which a PDZ domain forms a lid over a large internal cavity accessed through a proteolytic tunnel. Co-purifying peptides occupied two distinct substrate-binding sites, suggesting a coordinated recognition mechanism. Affinity pulldowns coupled with mass spectrometry identified several Bdellovibrio flagellins as candidate substrates, which were subsequently validated by biochemical assays and shown to be selectively degraded through recognition of a conserved C-terminal motif. A Bd0967-mCherry translational fusion localised to periplasmic foci during the intracellular predatory growth, consistent with flagellar resorption and flagellin turnover following prey invasion. Deletion of bd0967 caused developmental defects, including aberrant Bdellovibrio cell morphology and reduced predation efficiency. Together, these findings establish Bd0967 as a specialised CTP that couples flagellin degradation and developmental progression in a predatory bacterium.

biochemistry↗

A Type VII-secreted toxin enables inter-mycobacterial competition

Summary ParagraphMost bacteria live in complex environments where resources are scarce and competition is fierce. These organisms have evolved mechanisms to compete with other bacteria, often through the specialised secretion of proteinaceous toxins. Mycobacteria have not previously been reported to engage in this form of competition. The thick and unusual cell wall of mycobacteria, comprised of peptidoglycan, arabinogalactan and mycolic acids, is generally thought to be highly protective to these bacteria. Many enzymes have evolved to maintain this structure, including the GH183 family, which cleaves arabinogalactan. Here, we establish for the first time that some mycobacteria have weaponised a subset of these endo-D-arabinanases to enable inter-bacterial competition. We show that mycobacteria secrete an endo-D-arabinanase effector via the type VII secretion system that specifically targets the arabinogalactan layer of the Mycobacteriales cell envelope. Using structural biology and biochemistry, we identify the molecular basis for this activity and reveal a new protein family that protects the bacterium from the activity of this toxin. Finally, our data uncover widespread T7-secreted toxins in the Mycobacteriales, pointing to extensive inter-mycobacterial competition.

microbiology↗

TipA, a Bdellovibrio bacteriovorus BPI-like double-TULIP is opened by its adapter protein, TipB

Bdellovibrio bacteriovorus is a predatory bacterium that invades the periplasm of other Gram-negative bacteria and liberates prey biomolecules for replication. Bdellovibrio has a wealth of genes that encode unique proteins to enable this lifestyle. Using a series of x-ray structures, we show that the operonal pairing of bd2538 and bd2539, encode a double TULIP (tubular lipid binding protein) invasion protein A (TipA) and a small beta sandwich (TipB), respectively. TipA has a specialised N-terminal TULIP domain with a beta hairpin and helix that mediate homodimerisation through hairpin interdigitation. This dimerisation creates a large, continuous, enclosed lumen that we demonstrate to contain multiple lipid molecules. In addition, we show that TipB functions as a small adapter protein that binds to TipA using specialised loops that bury into the TipA hydrophobic core. This binding forms a clamp on the edge of the N-terminal beta sheet and induces a large 20 [A] conformational change, opening the TULIP fold to create an accessible interior. This study presents the first structural characterisation of lipid binding proteins in Bdellovibrio, and the first example of conformational change in TULIPs mediated by an adaptor protein. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/675085v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@3ef907org.highwire.dtl.DTLVardef@4f555dorg.highwire.dtl.DTLVardef@6d560forg.highwire.dtl.DTLVardef@2cfe49_HPS_FORMAT_FIGEXP M_FIG C_FIG Bdellovibrio bacteriovorus is a predatory bacterium that invades the periplasm of other Gram-negative bacteria in order to consume them from within. To enable this lifestyle, it has an arsenal of predation-associated genes, including the operonal pair bd2538 and bd2539. We use structural and biophysical techniques to characterise two proteins produced by these genes, TipA and TipB. O_LITipA is a double tubular lipid binding protein (TULIP) that forms a homodimer that sequesters lipids in its lumen and binds to lipid bilayers C_LIO_LITipB is a small beta sandwich that interacts with TipA via two specialised loops C_LIO_LIInteraction of TipA with TipB opens the TULIP fold of TipA C_LI

biochemistry↗

PNGaseA-mediated N-glycan stripping from peptides by infant-derived Bifidobacterium bifidum

N-glycans are highly common sources of nutrition for human colonic-dwelling bacteria. These microbes have evolved a several methods to remove N-glycans from proteins; herein we describe the biochemical and structural characterisation of one such enzyme, a PNGaseA superfamily member produced by the infant-associated Bifidobacterium bifidum LMG13195. This PNGase was demonstrated to elicit activity against a wide variety of N-glycan structures yet exhibited a high preference for N-glycans attached to a peptide rather than to a denatured or native protein. This unusual specificity highlights how bacterial species tune their enzymology to different types of substrates. The structural characterisation of this PNGase reveals how its structure determines this specificity while being the first structure presented from the PNGaseA superfamily, revealing a unique ten-stand {beta}-sheet cradling a canonical PNGase catalytic module.

biochemistry↗