title: High resolution crystallographic studies of alpha-hemolysin-phospholipid complexes define heptamer-lipid head group interactions: implication for understanding protein-lipid interactions.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA. galdiero@chemistry.unina.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Galdiero
authors.forename: Eric
authors.initials: E
authors.lastname: Gouaux
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods*; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D012680:Sensitivity and Specificity; D013211:Staphylococcus aureus / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D010743:Phospholipids; C021091:staphylococcal alpha-toxin