PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons
E-Collection

Hemolysin BL

PSI-SGKB [doi:10.3942/psi_sgkb/fm_2010_1]
Featured System - January 2010
Short description: Bacteria are master weapon makers.

Bacteria are master weapon makers. They must compete with other microorganisms for resources and they live in constant danger of being eaten and digested by larger animals, so many bacteria build powerful toxins to protect themselves. These toxins come in all shapes and sizes and seemingly attack every possible target in their foes. Three closely-related Bacillus species exemplify this diversity. Bacillus anthracis, the bacterium that causes anthrax, builds a three-part toxin that enters into cells and attacks the signaling apparatus, confounding the signals needed to orchestrate communication within the cell. The similar bacterium Bacillus thuringiensis builds a toxin that attacks insect cells, and is now sprayed on plants to act as a living insecticide. Bacillus cereus builds a different three-component toxin that attacks the cell membrane of intestinal cells, causing the miserable symptoms of food poisoning as our bodies try to flush it out.

A Pervasive Pest

Bacillus cereus is a bacterial jack-of-all-trades. Seemingly, it's happy almost anywhere. It is common in soil, where it grows and reproduces. When times get tough, it forms a weather-resistant spore and waits for better conditions. These spores find their way onto food of all sorts, and from there into our digestive system. The bacterium can also live in the intestine, along with the many other species of bacteria that inhabit us. Some strains of Bacillus cereus, however, build toxins like hemolysin BL that attack intestinal cells. These strains are thought to be a widespread cause of food poisoning, but this has been hard to quantify, since the symptoms are mild and pass quickly, and often are not reported to doctors.

Pore-forming Toxins

Hemolysin BL, like many other bacterial toxins, forms a pore through the membrane of cells, allowing ions and small molecules to leak out. Creating a pore with a soluble protein is a tricky proposition. The protein must be soluble enough that it can be built and exported from the bacterial cell, but then it must create a pore within the hydrophobic environment of the membrane. The solution used by many toxins is a switchblade mechanism. The portion of the toxin that penetrates the membrane is folded inside the soluble form of the protein, waiting to be deployed when the target cell is found.

B-component

Researchers at NYSGXRC have solved the structure of hemolysin BL toxin in its soluble state, available in PDB entry 2nrj. In this form, the toxin is ready to seek out a target cell and build its deadly pore. Most of the protein chain forms a large bundle of alpha helices. A small hairpin loop, colored yellow here, is thought to be the penetration mechanism. When it finds its target cell, this loop will unfold and enter the membrane. Then, as several copies of the toxin bind side-by-side, a pore is formed. The active toxin is actually composed of three separate components: the B subunit shown here, and two L subunits that assist with the construction of the pore. The similar hemolysin E from Escherichia coli cells (entry 1qoy at the PDB) shows one possible step in this switchblade action, where the small domain that includes the penetration loop has opened up before binding.

The JSmol tab below displays an interactive JSmol.

Neomycin Binding Site (PDB entry 2qbe and 2qbi

This Jmol image shows only a small section of the large ribosomal subunit (blue) along with ribosome recyclic factor (yellow) and the antibiotic neomycin (red). Two structures are shown--one that includes only RRF and the ribosome (PDB entry 2qbe), and one that includes the drug (PDB entry 2qbi). Use the buttons below to switch between the two structures, and notice that the drug distorts the RNA helix, pulling it away from RRF.

References

  1. Madegowda, M., Eswaramoorthy, S., Burley, S. K. and Swaminathan, S. (2008) X-ray crystal structure of the B component of Hemolysin BL from Bacillus cereus. Proteins 71, 534-540.

  2. Stenfors Arnesen, L. P., Fagerlund, A. and Granum, P. E. (2008) From soil to gut: Bacillus cereus and its food poisoning toxins. FEMS Microbiol. Rev. 32, 579-606.

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health