Structural elements of the cholesterol-dependent cytolysins that are responsible for their cholesterol-sensitive membrane interactions

被引:101
作者
Soltani, Casie E. [1 ]
Hotze, Eileen M. [1 ]
Johnson, Arthur E. [2 ,3 ,4 ]
Tweten, Rodney K. [1 ]
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA
[2] Texas A&M Univ, Hlth Sci Ctr, Dept Mol & Cellular Med, College Stn, TX 77843 USA
[3] Texas A&M Univ, Dept Chem & Biochem, College Stn, TX 77843 USA
[4] Texas A&M Univ, Dept Biophys, College Stn, TX 77843 USA
关键词
intermedilysin; perfringolysin; toxin; streptolysin; pneumolysin;
D O I
10.1073/pnas.0708104105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The pore-forming mechanism of the cholesterol-dependent cytolysins (CDCs) exhibits an absolute requirement for membrane cholesterol. The structural elements of the CDCs that mediate this interaction are not well understood. Three short hydrophobic loops (L1-L3) and a highly conserved undecapeptide sequence at the tip of domain 4 of the CDC structure are known to anchor the CDC to the membrane. It has been thought that the undecapeptide directly mediates the interaction of the CDCs with a cholesterol-rich cell surface. Herein we show that the L1-L3 loops, not the undecapeptide, are responsible for mediating the specific interaction of the CDCs with cholesterol-rich membranes. The membrane insertion of the undecapeptide was uncoupled from membrane binding by the covalent modification of the undecapeptide cysteine thiol. Modification of the cysteine prevented prepore to pore conversion, but did not affect membrane binding, thus demonstrating that undecapeptide membrane insertion follows that of the L1-L3 loops. These studies provide an example of a structural motif that specifically mediates the interaction of a bacterial toxin with a cholesterol-rich membrane.
引用
收藏
页码:20226 / 20231
页数:6
相关论文
共 45 条
[1]  
ALOUF JE, 2005, BACT TOXINS COMPREHE, P643
[2]  
BADIN J, 1978, CELL MOL BIOL, V23, P133
[3]   Lipid phase coexistence favors membrane insertion of equinatoxin-II, a pore-forming toxin from Actinia equina [J].
Barlic, A ;
Gutiérrez-Aguirre, I ;
Caaveiro, JMM ;
Cruz, A ;
Ruiz-Argüello, MB ;
Pérez-Gil, J ;
González-Mañas, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (33) :34209-34216
[4]   LYSIS OF PLEUROPNEUMONIA-LIKE ORGANSIMS BY STAPHYLOCOCCAL AND STREPTOCOCCAL TOXINS [J].
BERNHEIM.AW ;
DAVIDSON, M .
SCIENCE, 1965, 148 (3674) :1229-&
[5]   DISRUPTION OF WALL-LESS BACTERIA BY STREPTOCOCCAL AND STAPHYLOCOCCAL TOXINS [J].
BERNHEIMER, AW .
JOURNAL OF BACTERIOLOGY, 1966, 91 (05) :1677-+
[6]   Vibrio cholerae hemolysin -: Implication of amphiphilicity and lipid-induced conformational change for its pore-forming activity [J].
Chattopadhyay, K ;
Bhattacharyya, D ;
Banerjee, KK .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2002, 269 (17) :4351-4358
[7]   Vertical collapse of a cytolysin prepore moves its transmembrane β-hairpins to the membrane [J].
Czajkowsky, DM ;
Hotze, EM ;
Shao, ZF ;
Tweten, RK .
EMBO JOURNAL, 2004, 23 (16) :3206-3215
[8]  
DELATTRE J, 1979, CELL MOL BIOL, V24, P157
[9]   Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin [J].
Giddings, KS ;
Zhao, J ;
Sims, PJ ;
Tweten, RK .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2004, 11 (12) :1173-1178
[10]   Redefining cholesterol's role in the mechanism of the cholesterol's-dependent cytolysins [J].
Giddings, KS ;
Johnson, AE ;
Tweten, RK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (20) :11315-11320