The alpha-hemolysin is an archetypal pore-forming protein that is secreted from Staphylococcus aureus as a water-soluble monomer. When the monomer binds to the membrane of a susceptible cell, the membrane-bound molecules assemble into the lytic heptamer. Although a bilayer or a bilayer-like environment are essential to toxin assembly, there is no high resolution information on toxin-phospholipid complexes. We have determined the structures of detergent-solubilized alpha-hemolysin heptamer bound to glycerophosphocholine or dipropanoyl glycerophosphocholine at 1.75-1.80 A resolution and 110 K. The phosphocholine head group binds to each subunit in a crevice between the rim and the stem domains. The quaternary ammonium group interacts primarily with aromatic residues, whereas the phosphodiester moiety interacts with a conserved arginine residue. These structures provide a molecular basis for understanding why alpha-hemolysin preferentially assembles on membranes comprised of phosphocholine lipids.
High resolution crystal Structures of alpha-Hemolysin-phospholipid complexes define heptamer-lipid head group interactions: implication for understanding protein-lipid interactions / Galdiero, Stefania; E., Gouaux. - In: PROTEIN SCIENCE. - ISSN 0961-8368. - ELETTRONICO. - 13:6(2004), pp. 1503-1511.
High resolution crystal Structures of alpha-Hemolysin-phospholipid complexes define heptamer-lipid head group interactions: implication for understanding protein-lipid interactions
GALDIERO, STEFANIA
;
2004
Abstract
The alpha-hemolysin is an archetypal pore-forming protein that is secreted from Staphylococcus aureus as a water-soluble monomer. When the monomer binds to the membrane of a susceptible cell, the membrane-bound molecules assemble into the lytic heptamer. Although a bilayer or a bilayer-like environment are essential to toxin assembly, there is no high resolution information on toxin-phospholipid complexes. We have determined the structures of detergent-solubilized alpha-hemolysin heptamer bound to glycerophosphocholine or dipropanoyl glycerophosphocholine at 1.75-1.80 A resolution and 110 K. The phosphocholine head group binds to each subunit in a crevice between the rim and the stem domains. The quaternary ammonium group interacts primarily with aromatic residues, whereas the phosphodiester moiety interacts with a conserved arginine residue. These structures provide a molecular basis for understanding why alpha-hemolysin preferentially assembles on membranes comprised of phosphocholine lipids.File | Dimensione | Formato | |
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