High resolution crystallographic studies of α-hemolysin-phospholipid complexes define heptamer-lipid head group interactions: Implication for understanding protein-lipid interactions

Stefania Galdiero, Eric Gouaux

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The α-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 α-hemolysin heptamer bound to glycerophosphocholine or dipropanoyl glycerophosphocholine at 1.75-1.80 Å 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 α-hemolysin preferentially assembles on membranes comprised of phosphocholine lipids.

Original languageEnglish (US)
Pages (from-to)1503-1511
Number of pages9
JournalProtein Science
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 2004
Externally publishedYes

    Fingerprint

Keywords

  • Integral membrane protein
  • Pore-forming toxin
  • Protein-membrane interactions

ASJC Scopus subject areas

  • Biochemistry

Cite this