Rapid assembly of a multimeric membrane protein pore

Biophys J. 2011 Dec 7;101(11):2679-83. doi: 10.1016/j.bpj.2011.09.054.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / chemistry
  • Bacterial Toxins / metabolism*
  • Computer Simulation
  • Fluorescence
  • Hemolysin Proteins / chemistry
  • Hemolysin Proteins / metabolism*
  • Ion Channel Gating
  • Monte Carlo Method
  • Pore Forming Cytotoxic Proteins / chemistry
  • Pore Forming Cytotoxic Proteins / metabolism*
  • Protein Multimerization*
  • Protein Structure, Quaternary

Substances

  • Bacterial Toxins
  • Hemolysin Proteins
  • Pore Forming Cytotoxic Proteins
  • staphylococcal alpha-toxin