Rajesh Ramachandran1, Rodney K Tweten2
& Arthur E Johnson1, 3, 4
1
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
2
Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
3
Department of Medical Biochemistry and Genetics, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA.
4
Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
Correspondence should be addressed to Arthur E Johnson aejohnson@tamu.edu
Cholesterol-dependent cytolysins are bacterial protein toxins that bind to cholesterol-containing membranes, form oligomeric complexes and insert into the bilayer to create large aqueous pores. Membrane-dependent structural rearrangements required to initiate the oligomerization of perfringolysin O monomers have been identified, as have the monomer-monomer interaction surfaces, using site-specific mutagenesis, disulfide trapping and multiple fluorescence techniques. Upon binding to the membrane, a structural element in perfringolysin O moves to expose the edge of a previously hidden -strand that forms the monomer-monomer interface and is required for oligomer assembly. The -strands that form the interface each contain a single aromatic residue, and these aromatics appear to stack, thereby aligning the transmembrane -hairpins of adjacent monomers in the proper register for insertion. Collectively, these data reveal a novel membrane binding−dependent mechanism for regulating cytolysin monomer-monomer association and pore formation.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
-strand alignment
-strand that forms the monomer-monomer interface and is required for oligomer assembly. The 
