PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons
E-Collection

Related Articles
Community-Nominated Targets
July 2015
Drug Discovery: Solving the Structure of an Anti-hypertension Drug Target
July 2015
Retrospective: 7,000 Structures Closer to Understanding Biology
July 2015
Design and Evolution: Unveiling Translocator Proteins
June 2015
Signaling with DivL
May 2015
Signaling: A Platform for Opposing Functions
May 2015
Signaling: Securing Lipid-Protein Partnership
May 2015
Dynamic DnaK
March 2015
Iron-Sulfur Cluster Biosynthesis
December 2014
Mitochondrion: Flipping for UCP2
December 2014
Mitochondrion: Setting a New TRAP1
December 2014
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Quorum Sensing: E. coli Gets Involved
August 2014
iTRAQing the Ubiquitinome
July 2014
Microbiome: The Dynamics of Infection
September 2013
Protein-Nucleic Acid Interaction: A Modified SAM to Modify tRNA
July 2013
Protein-Nucleic Acid Interaction: Versatile Glutamate
July 2013
PDZ Domains
April 2013
Alpha-Catenin Connections
March 2013
Cell-Cell Interaction: A FERM Connection
March 2013
Cell-Cell Interaction: Magic Structure from Microcrystals
March 2013
Cell-Cell Interaction: Modulating Self Recognition Affinity
March 2013
Bacterial Hemophores
January 2013
Archaeal Lipids
December 2012
Membrane Proteome: Capturing Multiple Conformations
December 2012
Lethal Tendencies
October 2012
Symmetry from Asymmetry
October 2012
A signal sensing switch
September 2012
Regulatory insights
September 2012
AlkB Homologs
August 2012
Budding ensemble
August 2012
Targeting Enzyme Function with Structural Genomics
July 2012
The machines behind the spindle assembly checkpoint
June 2012
Chaperone interactions
April 2012
Pilus Assembly Protein TadZ
April 2012
Revealing the Nuclear Pore Complex
March 2012
Topping off the proteasome
March 2012
Twist to open
March 2012
Disordered Proteins
February 2012
Analyzing an allergen
January 2012
Making Lipopolysaccharide
January 2012
Pulling on loose ends
January 2012
Terminal activation
December 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
TLR4 regulation: heads or tails?
October 2011
Ribose production on demand
September 2011
Moving some metal
August 2011
Looking for lipids
July 2011
Ribofuranosyl Binding Protein
June 2011
A molecular switch for neuronal growth
May 2011
Cell wall recycler
May 2011
Added benefits
April 2011
NMR challenges current protein hydration dogma
March 2011
Nitrile Reductase QueF
March 2011
Tip formin
March 2011
Inhibiting factor
February 2011
PASK staying active
February 2011
Tryptophanyl-tRNA Synthetase
February 2011
Regulating nitrogen assimilation
January 2011
Subtle shifts
January 2011
Nitrobindin
December 2010
Function following form
October 2010
tRNA Isopentenyltransferase MiaA
August 2010
Importance of extension for integrin
June 2010
Phytochrome
April 2010
Alg13 Subunit of N-Acetylglucosamine Transferase
February 2010
Hemolysin BL
January 2010
Secretagogin
December 2009
Two-component signaling
December 2009
Network coverage
November 2009
Pseudouridine Synthase TruA
November 2009
Unusual cell division
October 2009
Toxin-antitoxin VapBC-5
September 2009
Salicylic Acid Binding Protein 2
August 2009
Proofreading RNA
July 2009
Ykul structure solves bacterial signaling puzzle
July 2009
Hda and DNA Replication
June 2009
Controlling p53
May 2009
Mitotic checkpoint control
May 2009
Ribonuclease and Ribonuclease Inhibitor
April 2009
The elusive helicase
April 2009
Aquaglyceroporin
March 2009
High-energy storage system
February 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Poly(A) RNA recognition
January 2009
Activating BAX
December 2008
Scavenger Decapping Enzyme DcpS
November 2008
Bacteriophage Lambda cII Protein
October 2008
New metal-binding domain
October 2008
Blocking AmtB
September 2008
T-Rex
September 2008
Aspartate Dehydrogenase
August 2008
RNase T
July 2008
Chronophin
May 2008

Research Themes Cell biology

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