Abstract
In addition to multiple virulence factors, Bacillus cereus a pathogen that causes food poisoning and life-threatening wound infections, secretes the pore-forming toxin hemolysin II (HlyII). The HlyII toxin has a unique 94 amino acid C-terminal domain (HlyIIC). HlyIIC exhibits splitting of NMR resonances due to cis/trans isomerization of a single proline near the C-terminus. To overcome heterogeneity, we solved the structure of P405M-HlyIIC, a mutant that exclusively stabilizes the trans state. The NMR structure of HlyIIC reveals a novel fold, consisting of two subdomains αA-β1-β2 and β3-β4-αB-β5, that come together in a barrel-like structure. The barrel core is fastened by three layers of hydrophobic residues. The barrel end opposite the HlyIIC-core has a positively charged surface, that by binding negatively charged moieties on cellular membranes, may play a role in target-cell surface recognition or stabilization of the heptameric pore complex. In the WT domain, dynamic flexibility occurs at the N-terminus and the first α-helix that connects the HlyIIC domain to the HlyII-core structure. In the destabilizing P405M mutant, increased flexibility is evident throughout the first subdomain, suggesting that the HlyIIC structure may have arisen through gene fusion.
Highlights
The soil-dwelling, spore-forming B. cereus bacterium[1,2,3] produces a number of virulence factors[4] including several secreted pore-forming toxins (PFTs) that form lytic channels in the membranes of target cells[5]
The present work demonstrates that hemolysin II (HlyII) contains a structurally unique C-terminal domain, not present on PFTs that otherwise share structural homology and similar function
The structure of HlyIIC, which consists of two β-sheets flanked by two α-helices in a barrel-like structure, represents a novel fold with no identifiable structural homologs
Summary
The soil-dwelling, spore-forming B. cereus bacterium[1,2,3] produces a number of virulence factors[4] including several secreted pore-forming toxins (PFTs) that form lytic channels in the membranes of target cells[5]. One of these toxins, hemolysin II (HlyII), is present in several closely related Bacillus species including B. cereus, B. thuringiensis (a bacterium that parasitizes insects and has insecticide applications), and B. anthracis (the cause of anthrax)[6, 7]. The NMR studies define the structural and dynamic properties of the HlyIIC domain and serve as a starting point for understanding its possible functions
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