TY - JOUR
T1 - α-Hemolysin from Staphylococcus aureus
T2 - An archetype of β-barrel, channel-forming toxins
AU - Gouaux, Eric
PY - 1998/1/1
Y1 - 1998/1/1
N2 - 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.
AB - 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.
KW - Bacterial toxin
KW - Heptamer
KW - Membrane protein
KW - Transmembrane channels
KW - α- toxin
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U2 - 10.1006/jsbi.1998.3959
DO - 10.1006/jsbi.1998.3959
M3 - Article
C2 - 9615434
AN - SCOPUS:0031877366
VL - 121
SP - 110
EP - 122
JO - Journal of Structural Biology
JF - Journal of Structural Biology
SN - 1047-8477
IS - 2
ER -