Structure of Staphylococcal α-Hemolysin, a Heptameric Transmembrane Pore

Abstract

The structure of the Staphylococcus aureus alpha-hemolysin pore has been determined to 1.9 A resolution. Contained within the mushroom-shaped homo-oligomeric heptamer is a solvent-filled channel, 100 A in length, that runs along the sevenfold axis and ranges from 14 A to 46 A in diameter. The lytic, transmembrane domain comprises the lower half of a 14-strand antiparallel beta barrel, to which each protomer contributes two beta strands, each 65 A long. The interior of the beta barrel is primarily hydrophilic, and the exterior has a hydrophobic belt 28 A wide. The structure proves the heptameric subunit stoichiometry of the alpha-hemolysin oligomer, shows that a glycine-rich and solvent-exposed region of a water-soluble protein can self-assemble to form a transmembrane pore of defined structure, and provides insight into the principles of membrane interaction and transport activity of beta barrel pore-forming toxins.

Characterization of Nucleic Acids by Nanopore Analysis

“…All three homopolymers exhibited a linear relation between chain length and duration of the blockade. For RNA molecules, the fastest is polyC (∼2 µs/base), poly A is The hemolysin nanopore is shown in cross section, based on the X-ray data of Song et al 19 An ionic current of KCl is driven by the applied voltage through the open pore on the left. Under these conditions, ionic polymers such as nucleic acids are captured by the standing electrical field and driven through the pore.…”

“…Song et al 19 reported the crystal structure of R-hemolysin at atomic resolution, and their data were used to prepare the space-filling model shown in Figure 5. The entrance to the channel has a diameter of approximately 2.6 nm that contains a ring of threonine residues.…”

Cytotoxicity of Bacillus thuringiensis Cry1Ab toxin depends on specific binding of the toxin to the cadherin receptor BT-R1 expressed in insect cells

“…[4][5][6][7][8] X-ray crystallographic studies have shown that toxin oligomer complexes most likely assemble in b-barrel or umbrella-like channels in lipid membranes. [9][10][11][12] However, the involvement of such oligomers in cell death is not well understood because most toxin oligomer complexes themselves apparently do not punch holes in membrane and do not simply cause cell death by lysis. 13,14 Instead, the interaction of toxins with cells involves complicated pathways, the end result of which is cell death.…”

Dendrimers in Nanoscale Confinement: The Interplay between Conformational Change and Nanopore Entrance

“…Second, the PAMAM dendrimer and the αHL pore have matching nanoscale dimensions ( Figure 1). 35 Finally, the pore lumen at the trans side is of simple cylindrical shape, which was anticipated to facilitate studying the interaction with PAMAM. In particular, at the trans side, the αHL pore features a cylinderlike transmembrane β-barrel of approximately 2 nm inner width and 5.0 nm height, which narrows to a 1.2 nm-wide inner constriction ( Figure 1A).…”