Article
- The EMBO Journal (2004) 23, 3206 - 3215
- doi:10.1038/sj.emboj.7600350
Published online: 5 August 2004
Subject Categories:
Vertical collapse of a cytolysin prepore moves its transmembrane 
-hairpins to the membrane
Daniel M Czajkowsky1, Eileen M Hotze2, Zhifeng Shao1 and Rodney K Tweten2
- Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA, USA
- Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Correspondence to:
Zhifeng Shao, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Room 480, Jordan Hall, Charlottesville, VA 22908, USA. Tel.: +1 434 982 0829; Fax: +1 434 982 1616; E-mail: zs9q@virginia.edu
Rodney K Tweten, Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, 940 Stanton L Young Blvd, Oklahoma City, 73104, USA. Tel.: +1 405 271 1205x1; Fax: +1 405 271 3117; E-mail: rod-tweten@ouhsc.edu
Received 25 May 2004; Accepted 8 July 2004
Abstract
Perfringolysin O (PFO) is a prototype of the large family of pore-forming cholesterol-dependent cytolysins (CDCs). A central enigma of the cytolytic mechanism of the CDCs is that their membrane-spanning 
-hairpins (the transmembrane amphipathic -hairpins (TMHs)) appear to be 
40 Å too far above the membrane surface to cross the bilayer and form the pore. We now present evidence, using atomic force microscopy (AFM), of a significant difference in the height by which the prepore and pore protrude from the membrane surface: 113
5 Å for the prepore but only 735 Å for the pore. Time-lapse AFM micrographs show this change in height in real time. Moreover, the monomers in both complexes exhibit nearly identical surface features and these results in combination with those of spectrofluorimetric analyses indicate that the monomers remain in a perpendicular orientation to the bilayer plane during this transition. Therefore, the PFO undergoes a vertical collapse that brings its TMHs to the membrane surface so that they can extend across the bilayer to form the -barrel pore.
Keywords:
- AFM,
- perfringolysin,
- pore,
- toxin
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