Pore forming toxin, α-hemolysin
From Proteopedia
α-Hemolysin from Staphlococcus aureus is a pore-forming toxin made of seven repeats of an identical monomer arranged in a ring. The structural basis of the toxic activity was readily revealed when the structure of the ring was solved.
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ALPHA-HEMOLYSIN FROM STAPHYLOCOCCUS AUREUS
The structure of the Staphylococcus aureus alpha-hemolysin pore has been determined to 1.9 A resolution. Contained within the mushroom-shaped homo-oligomeric heptamer is a solvent-filled channel, 100 A in length, that runs along the sevenfold axis and ranges from 14 A to 46 A in diameter. The lytic, transmembrane domain comprises the lower half of a 14-strand antiparallel beta barrel, to which each protomer contributes two beta strands, each 65 A long. The interior of the beta barrel is primarily hydrophilic, and the exterior has a hydrophobic belt 28 A wide. The structure proves the heptameric subunit stoichiometry of the alpha-hemolysin oligomer, shows that a glycine-rich and solvent-exposed region of a water-soluble protein can self-assemble to form a transmembrane pore of defined structure, and provides insight into the principles of membrane interaction and transport activity of beta barrel pore-forming toxins.
Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore., Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE, Science. 1996 Dec 13;274(5294):1859-66. PMID:8943190
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Background
This is just to show an example review citation[1].
About this Structure
Template:STRUCTURE 7ahl====The α-hemolysin oligomer==== α-hemolysin (7ahl) is from Staphylococcus aureus.
Each chain in the oligomeric complex is ; the other monomers are translucent to emphasize one of the seven monomers. Note the seven-fold rotational symmetry. .
Seven monomers come together in a ring, with . .
α-hemolysin interaction with the membrane
, α-hemolysin's stalk is perfectly designed to span the plasma membrane of eukaryotic cells (ca. 2.5 nm or 25 Å). A fancier version of this scene is below.
[Note: the following view generates a substantial surface which may take several minutes to calculate. Use the one above as an alternative unless you are willing to spend the time.], α-hemolysin's stalk is perfectly designed to span the plasma membrane of eukaryotic cells (ca. 2.5 nm or 25 Å).
Unlike the polar surface of more typical proteins, , and is instead lipophilic or preferring to be in a lipid environment.
which is largely polar since it would sit outside the cell.
KEY: Polar Hydrophobic
To help give a better idea of how α-hemolysin interacts with the membrane lipid bilayer, as calculated by the Orientations of Proteins in Membranes database(University of Michigan, USA) is shown with the red patch of spheres indicating the boundary of the hydrophobic core closet to the outside of the cell and the blue patch of spheres indicating the boundary closest to the inside of the cell.
The α-hemolysin pore
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| 7ahl, resolution 1.89Å (). | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
[Note: the following view generates a substantial surface which may take several minutes to calculate. Be patient.] Displaying the surface illustrates clearly that there is , which is structural explanation for why these have . Such pores are expectedly detrimental to the cell, allowing exodus of critical molecules, destroying the established membrane potential and ionic gradients, and contributing to osmotic swelling. .
PDB entry
7ahl is a 7 chain structure of sequences from Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference for the structure
- Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science. 1996 Dec 13;274(5294):1859-66. PMID:8943190
Notes and Literature References
Additional Literature and Resources
David Briggs's Blog on α-hemolsyin, which served as a template for the original adaptation of 7ahl to this topic page.
Pore-forming toxin at Wikipedia
Page on Bacterial Toxin α-Hemolysin by Aleksei Aksimentiev and Klaus Schulten
Page started with original page seeded by OCA on Mon Feb 16 13:00:23 2009 for 7ahl
