title: Rapid assembly of a multimeric membrane protein pore.
abstract: We have observed the assembly of the staphylococcal pore-forming toxin α-hemolysin using single-molecule fluorescence imaging. Surprisingly, assembly from the monomer to the complete heptamer is extremely rapid, occurring in <5 ms. No lower order oligomeric intermediates are detected. Monte Carlo simulation of our experiment shows that assembly is diffusion limited, and pore formation is dependent on the stability of intermediate species. There are close similarities between bacterial pore-forming toxins, such as staphylococcal α-hemolysin, the anthrax protective antigen, and the cholesterol-dependent cytolysins, and their eukaryotic analogs, such as the complement pore membrane attack complex and perforin domain. The assembly mechanism we have observed for α-hemolysin provides a simple model that aids our understanding of these important pore formers.
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: James R
authors.initials: JR
authors.lastname: Thompson
authors.forename: Bríd
authors.initials: B
authors.lastname: Cronin
authors.forename: Hagan
authors.initials: H
authors.lastname: Bayley
authors.forename: Mark I
authors.initials: MI
authors.lastname: Wallace
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D005453:Fluorescence; D006460:Hemolysin Proteins / Q000737:chemistry / Q000378:metabolism*; D015640:Ion Channel Gating; D009010:Monte Carlo Method; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D052899:Pore Forming Cytotoxic Proteins; C021091:staphylococcal alpha-toxin