alpha-Hemolysin from Staphylococcus aureus: an archetype of beta-barrel, channel-forming toxins.
alpha-Hemolysin, secreted from Staphylococcus aureus as a water-soluble monomer of 33.2 kDa, assembles on cell membranes to form transmembrane, heptameric channels. The structure of the detergent-solubilized heptamer has been determined by X-ray crystallography to 1.9 A resolution. The heptamer has a mushroom-like shape and measures up to 100 A in diameter and 100 A in height. Spanning the length of the molecule and coincident with the molecular sevenfold axis is a water-filled channel that ranges in diameter from approximately 16 to approximately 46 A. A 14 strand antiparallel beta-barrel, in which two strands are contributed by each subunit, defines the transmembrane domain. On the exterior of the beta-barrel there is a hydrophobic belt approximately 30 A in width that provides a surface complementary to the nonpolar portion of the lipid bilayer. The extensive promoter-protomer interfaces are composed of both salt-links and hydrogen bonds, as well as hydrophobic interactions, and these contacts provide a molecular rationalization for the stability of the heptamer in SDS solutions up to 65 degrees C. With the structure of the heptamer in hand, we can better understand the mechanisms by which the assembled protein interacts with the membrane and can postulate mechanisms of assembly.
Gouaux
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Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000494:pharmacology; D007473:Ion Channels / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011108:Polymers; D011487:Protein Conformation; D015202:Protein Engineering; D017510:Protein Folding; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D013211:Staphylococcus aureus / Q000737:chemistry*
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D007473:Ion Channels; D011108:Polymers; C021091:staphylococcal alpha-toxin