The Unique Molecular Choreography of Giant Pore Formation by the Cholesterol-Dependent Cytolysins of Gram-Positive Bacteria.
The mechanism by which the cholesterol-dependent cytolysins (CDCs) assemble their giant β-barrel pore in cholesterol-rich membranes has been the subject of intense study in the past two decades. A combination of structural, biophysical, and biochemical analyses has revealed deep insights into the series of complex and highly choreographed secondary and tertiary structural transitions that the CDCs undergo to assemble their β-barrel pore in eukaryotic membranes. Our knowledge of the molecular details of these dramatic structural changes in CDCs has transformed our understanding of how giant pore complexes are assembled and has been critical to our understanding of the mechanisms of other important classes of pore-forming toxins and proteins across the kingdoms of life. Finally, there are tantalizing hints that the CDC pore-forming mechanism is more sophisticated than previously imagined and that some CDCs are employed in pore-independent processes.
Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; email: Rod-Tweten@ouhsc.edu.
Rodney K
RK
Tweten
Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; email: Rod-Tweten@ouhsc.edu.
Eileen M
EM
Hotze
Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; email: Rod-Tweten@ouhsc.edu.
Kristin R
KR
Wade
D001427:Bacterial Toxins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003603:Cytotoxins / Q000737:chemistry; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary
D001427:Bacterial Toxins; D003603:Cytotoxins; D052899:Pore Forming Cytotoxic Proteins; D002784:Cholesterol
CD59; intermedilysin; perfringolysin O; sterol; streptolysin O; β-barrel