The Crystal Structure of Bacillus cereus HblL1

Worthy, Harley L.; Williamson, Lainey J.; Auhim, Husam Sabah; Leppla, Stephen H.; Sastalla, Inka; Jones, D. Dafydd; Rizkallah, P.J.; Berry, Colin

doi:10.3390/toxins13040253

Cited by 10 publications

(5 citation statements)

References 44 publications

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“…Ganash et al (2013) speculated that the Nhe trimer requires interaction with unknown proteins of an additional function [37]. A specific binding order of the three Nhe and Hbl components is also necessary for pore formation [51,52]. We found that NheB and Hbl-L 1 were close to NheA and Hbl-B in the predicted trimer structure.…”

Section: Discussionmentioning

confidence: 69%

Phylogenetic and protein prediction analysis reveals the taxonomically diverse distribution of virulence factors in the Bacillus cereus group

Zhang

Yin

et al. 2022

Preprint

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Bacillus cereus is a food contaminant with widely varying enterotoxic potential of its virulence proteins. In this article, phylogenetic analysis of the whole-genome amino acid sequences of 41 strains, evolutionary distance calculation of the amino acid sequences of the virulence genes, and functional and structural prediction of the virulence proteins were performed to reveal the taxonomically diverse distribution of virulence factors. The genome evolution of the strains showed a clustering trend based on the coding virulence genes. The strains of B. cereus have evolved into non-toxic risk and toxic risk clusters with medium-high- and medium-low-risk clusters. The distances of evolutionary transfer relative to housekeeping genes of incomplete virulence genes were greater than those of complete virulence genes, and the distance values of HblACD were higher than those of nheABC and CytK among the complete virulence genes. Cytoplasmic localization was impossible for all the virulence proteins, and NheB, NheC, Hbl-B, and Hbl-L 1 were extracellular according to predictive analysis. Nhe and Hbl proteins except CytK had similar spatial structures. The predicted structures of Nhe and Hbl mainly showed ‘head’ and ‘tail’ domains. The ‘head’ of NheA and Hbl-B, including two α-helices separated by β-tongue strands, might play a special role in Nhe trimers and Hbl trimers, respectively. The ‘cap’ of CytK, which includes two ‘latches’ with many β-sheets, formed a β-barrel structure with pores, and a ‘rim’ balanced the structure. The evolution of B. cereus strains showed a clustering tendency based on the coding virulence genes, and the complete virulence-gene operon combination had higher relative genetic stability. The beta-tongue or latch associated with β-sheet folding might play an important role in the binding of virulence structures and pore-forming toxins in B. cereus .

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Section: Discussionmentioning

confidence: 69%

Phylogenetic and protein prediction analysis reveals the taxonomically diverse distribution of virulence factors in the Bacillus cereus group

Zhang

Yin

et al. 2022

Preprint

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“…To assess the structural stability of modelled Cry48Aa1-Tpp49Aa1 complexes, molecular dynamics (MD) simulations were performed using GROMACS (v.2020.1) 47 on Cardiff University’s High-Performance Computing cluster, Hawk. Set-up, energy minimisation, equilibration, and production simulations were performed as previously described 48 . Production simulations were performed for 100 ns and the resulting trajectories were visualised.…”

Section: Methodsmentioning

confidence: 99%

Structure of theLysinibacillus sphaericusTpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX

Williamson

Galchenkova

Best

et al. 2022

Preprint

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Tpp49Aa1 from Lysinibacillus sphaericus is a Toxin_10 family protein that must interact with Cry48Aa1, a 3-domain crystal protein, to produce potent mosquitocidal activity, specifically against Culex quinquefasciatus mosquitoes. We use Culex cell lines to demonstrate for the first time transient detrimental effects of individual toxin components and widen the known target range of the proteins. MHz serial femtosecond crystallography at a nano-focused X-ray free electron laser allowed rapid and high-quality data collection to determine the Tpp49Aa1 structure at 2.2 Å resolution from the merged X-ray diffraction data. The structure revealed the packing of Cry49Aa1 within the natural nanocrystals isolated from sporulated bacteria, as a homodimer with a large intermolecular interface. We then modelled the potential interaction between Tpp49Aa1 and Cry48Aa1. The structure sheds light on natural crystallisation and, along with cell-based assays broadens our understanding of this two-component system.

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“…HBL toxin comprises three subunits: HBL-B, HBL-L1, and HBL-L2, encoded by the genes hblA, hblD , and hblC , respectively. 13 , 14 These three genes are located on the operon hblCDAB , and the promoter is located upstream of hblC . 15 Alignment of the deduced amino acid sequences of the three proteins indicates significant similarity (20 to 24% identical), and structural analysis of the HBL protein shows that all three components are almost entirely composed of α-helices.…”

Section: Introductionmentioning

confidence: 99%

Pore-Forming Toxins During Bacterial Infection: Molecular Mechanisms and Potential Therapeutic Targets

Hu¹,

Liu²,

Sun³

2021

DDDT

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Bacterial infections are predominantly treated with antibiotics, and resistance to antibiotics is becoming an increasing threat to our health. Pore-forming toxins (PFTs) are virulence factors secreted by many pathogenic bacterial strains, both in acute and chronic infections. They are special membrane-targeting proteins that exert toxic effects by forming pores in the cell membrane. Recent studies have elucidated the structure of PFTs and the detailed molecular mechanisms of their pathogenicity. Here, we discuss recent findings that highlight the regulatory mechanisms and important roles of two types of PFTs, α-PFTs and β-PFTs, in mediating the virulence of bacteria, and the therapeutic potential of targeting PFTs for antibacterial treatment. Therapeutic strategies based on PFTs are highly specific and may alleviate the issue of increasing resistance to antibiotics.

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The Crystal Structure of Bacillus cereus HblL1

Cited by 10 publications

References 44 publications

Phylogenetic and protein prediction analysis reveals the taxonomically diverse distribution of virulence factors in the Bacillus cereus group

Phylogenetic and protein prediction analysis reveals the taxonomically diverse distribution of virulence factors in the Bacillus cereus group

Structure of theLysinibacillus sphaericusTpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX

Pore-Forming Toxins During Bacterial Infection: Molecular Mechanisms and Potential Therapeutic Targets

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