Structure of Staphylococcal α-Hemolysin, a Heptameric Transmembrane Pore

  title={Structure of Staphylococcal $\alpha$-Hemolysin, a Heptameric Transmembrane Pore},
  author={Langzhou Song and Michael R. Hobaugh and C. Shustak and Stephen Cheley and Hagan Bayley and J. Eric Gouaux},
  pages={1859 - 1865}
The structure of the Staphylococcus aureus α-hemolysin pore has been determined to 1.9 Å resolution. Contained within the mushroom-shaped homo-oligomeric heptamer is a solvent-filled channel, 100 Å in length, that runs along the sevenfold axis and ranges from 14 Å to 46 Å in diameter. The lytic, transmembrane domain comprises the lower half of a 14-strand antiparallel β barrel, to which each protomer contributes two β strands, each 65 Å long. The interior of the β barrel is primarily… 

α-Hemolysin fromStaphylococcus aureus:An Archetype of β-Barrel, Channel-Forming Toxins

α-Hemolysin, secreted fromStaphylococcus aureusas a water-soluble monomer of 33.2 kDa, assembles on cell membranes to form transmembrane, heptameric channels. The structure of the

Crystal structure of the octameric pore of staphylococcal γ-hemolysin reveals the β-barrel pore formation mechanism by two components

The crystal structure of the octameric pore form of γ-hemolysin at 2.5 Å resolution is reported, which is the first high-resolution structure of a β-barrel transmembrane protein composed of two proteins reported to date.

Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins.

Crystal structures of staphylococcal γ-haemolysin and leucocidin prepores suggest a two-step transmembrane β-barrel pore formation mechanism in which the upper extramembrane and bottom trans Membrane regions are formed independently.

Preliminary X-ray crystallographic study of staphylococcal α-haemolysin monomer.

  • T. SugawaraD. Yamashita M. Yao
  • Chemistry
    Acta crystallographica. Section F, Structural biology and crystallization communications
  • 2013
The relative orientation among molecules was distinct from that of the pore, indicating that the crystal contained monomeric α-haemolysin, which is a β-barrel pore-forming toxin expressed by Staphylococcus aureus.

Crystal structure of Staphylococcal LukF delineates conformational changes accompanying formation of a transmembrane channel

The LukF structure illustrates how a channel–forming toxin masks protein–protein and protein–membrane interfaces prior to cell binding and assembly, and together with the α–hemolysin heptamer structure, they define the end points on the pathway of toxin assembly.

Structure-Function Relationships of a Novel Bacterial Toxin, Hemolysin E

Gel filtration analyses suggested that immobilizing αG inhibits HlyE activity at a late stage of pore formation, whereas in solution it prevents aggregation and consequent inactivation.

Distinction between Pore Assembly by Staphylococcal α-Toxin versus Leukotoxins

Modifications of bipartite leukotoxins by two different processes, using fusion with glutathione S-transferase and bridging of the N-terminal extremity to the adjacent β-sheet via disulphide bridges, are not deleterious for biological activity and illustrate a microheterogeneity of the structural organizations between bipartites and α-toxin.

Subunit Dimers of α-Hemolysin Expand the Engineering Toolbox for Protein Nanopores*

The ability to incorporate subunit dimers into αHL pores increases the range of structures that can be obtained from engineered protein nanopores, and changes the stoichiometry of the central pore of αHL by the concatenation of subunits.



Subunit stoichiometry of staphylococcal alpha-hemolysin in crystals and on membranes: a heptameric transmembrane pore.

  • J. GouauxO. Braha H. Bayley
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
It is reported that analysis of x-ray diffraction data and chemical modification experiments indicate that the alpha HL oligomer is a heptamer, and data establish the hePTameric oligomerization state of thealpha HL transmembrane pore both in three-dimensional crystals and on a biological membrane.

A pore-forming protein with a metal-actuated switch.

It is shown that when five consecutive histidine residues replace amino acids 130-134 at the midpoint of the loop, they provide a switch with which pore activity can be turned off by micromolar concentrations of divalent zinc ions and turned on with the chelating agent EDTA.

Secondary structure and assembly mechanism of an oligomeric channel protein.

By chemical cross-linking, it is confirmed that the major form of the channel is a hexamer, and the circular dichroism spectrum of this hexamer in detergent revealed that it contains a high proportion of beta-sheet that must lie within the lipid bilayer when the protein is associated with membranes.

Restoration of pore-forming activity in staphylococcal alpha-hemolysin by targeted covalent modification.

It is shown that modification of the inactive single-cysteine mutant alpha HL-H35C with iodoacetamide, to form H35CamC, generates significant pore-forming activity.

Molecular architecture of a toxin pore: a 15‐residue sequence lines the transmembrane channel of staphylococcal alpha‐toxin.

Staphylococcus aureus alpha‐toxin is a hydrophilic polypeptide of 293 amino acids that produces heptameric transmembrane pores that persists after the removal of membrane lipids and hence probably reflects protomer‐protomer contacts within theheptamer.

Key Residues for Membrane Binding, Oligomerization, and Pore Forming Activity of Staphylococcal α-Hemolysin Identified by Cysteine Scanning Mutagenesis and Targeted Chemical Modification (*)

Through detailed examination of the phenotypes of the mutant and modified hemolysins, this study has pinpointed residues and regions in the αHL polypeptide chain that are important for binding to rRBC, oligomer formation and pore activity.

Identification of a putative membrane-inserted segment in the alpha-toxin of Staphylococcus aureus.

A model in which the central region of the alpha-toxin inserts into the membrane and possibly participates in forming the wall of the pore is proposed.