Structural features of the pore formed by Staphylococcus aureus alpha-toxin inferred from chemical modification and primary structure analysis.
Staphylococcus aureus alpha-toxin makes cells and model membranes permeable to ions and uncharged molecules by opening oligomeric pores of uniform size. Its primary sequence reveals peculiar features which give some hints on the structure of the pore. A flexible region separating the toxin into two halves, several amphiphilic beta-strands and two amphiphilic alpha-helices long enough to span the hydrophobic core of the lipid bilayer are predicted. In analogy to bacterial porins, we propose that the inner walls of the pore are, at least in part, built by an amphiphilic beta-barrel. The model is consistent with circular dichroism data and with the electrophysiological properties of the pore. Functional information on this toxin were obtained by chemical modification of its four histidine residues. Specific carbethoxylation suggested they have different roles: one is required for specific receptor binding, one for oligomerisation and two for unspecific lipid binding. A tentative assignment of each histidine to its specific role is done on the basis of the structural predictions. A functionally related hemolysin, Aeromonas hydrophyla aerolysin, reveals remarkably similar features including the presence and location of histidines involved in receptor binding and oligomerisation.
Menestrina
G
G
Dipartimento di Fisica, Università di Trento, Italy.
Belmonte
G
G
Parisi
V
V
Morante
S
S
D001427:Bacterial Toxins / Q000737:chemistry* / Q000633:toxicity; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000633:toxicity; D006639:Histidine; D007473:Ion Channels / Q000187:drug effects*; D052899:Pore Forming Cytotoxic Proteins; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D007473:Ion Channels; D052899:Pore Forming Cytotoxic Proteins; C021091:staphylococcal alpha-toxin; D006639:Histidine; C032676:aerolysin