α-Hemolysin from Staphylococcus aureus: An archetype of β-barrel, channel-forming toxins

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Abstract

α-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 Å resolution. The heptamer has a mushroom-like shape and measures up to 100 in diameter and 100 Å 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 ~16 to ~46 Å. A 14 strand antiparallel β-barrel, in which two strands are contributed by each subunit, defines the transmembrane domain. On the exterior of the β-barrel there is a hydrophobic belt approximately 30 Å in width that provides a surface complementary to the nonpolar portion of the lipid bilayer. The extensive protomer-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°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.

Original languageEnglish (US)
Pages (from-to)110-122
Number of pages13
JournalJournal of Structural Biology
Volume121
Issue number2
DOIs
StatePublished - Jan 1 1998

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Keywords

  • Bacterial toxin
  • Heptamer
  • Membrane protein
  • Transmembrane channels
  • α- toxin

ASJC Scopus subject areas

  • Structural Biology

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