All major cholesterol-dependent cytolysins use glycans as cellular receptors
Lucy K Shewell, Christopher J Day, Freda E-C Jen, Thomas Haselhorst, John M Atack, Josephine F Reijneveld, Arun Everest-Dass, David B A James, Kristina M Boguslawski, Stephan Brouwer, Christine M Gillen, Zhenyao Luo, Bostjan Kobe, Victor Nizet, Mark von Itzstein, Mark J Walker, Adrienne W Paton, James C Paton, Victor J Torres, Michael P Jennings
Applications: SPR
Reactive species: Human
"Abstract: Cholesterol-dependent cytolysins (CDCs) form pores in cholesterol-rich membranes, but cholesterol alone is insufficient to explain their cell and host tropism. Here, we show that all eight major CDCs have high-affinity lectin activity that identifies glycans as candidate cellular receptors. Streptolysin O, vaginolysin, and perfringolysin O bind multiple glycans, while pneumolysin, lectinolysin, and listeriolysin O recognize a single glycan class. Addition of exogenous carbohydrate receptors for each CDC inhibits toxin activity. We present a structure for suilysin domain 4 in complex with two distinct glycan receptors, P1 antigen and αGal/Galili. We report a wide range of binding affinities for cholesterol and for the cholesterol analog pregnenolone sulfate and show that CDCs bind glycans and cholesterol independently. Intermedilysin binds to the sialyl-TF O-glycan on its erythrocyte receptor, CD59. Removing sialyl-TF from CD59 reduces intermedilysin binding. Glycan-lectin interactions underpin the cellular tropism of CDCs and provide molecular targets to block their cytotoxic activity."
Article snippet: Removal of N-linked sLeX from Mac-1 was achieved by incubation with peptide N-glycosidase F (PNGase F) (*) and confirmed by SPR analysis with anti-sLeX monoclonal antibody(clone 258-12767, Creative Diagnostics). 
Figure 1. A subset of SPR results for CDCs against glycans plus cholesterol and PS.
COA
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