Structure of the lectin regulatory domain of the cholesterol-dependent cytolysin lectinolysin reveals the basis for its lewis antigen specificity

SC Feil; S Lawrence; TD Mulhern; JK Holien; EM Hotze; S Farrand; RK Tweten; MW Parker

Journal article

Structure of the lectin regulatory domain of the cholesterol-dependent cytolysin lectinolysin reveals the basis for its lewis antigen specificity

SC Feil, S Lawrence, TD Mulhern, JK Holien, EM Hotze, S Farrand, RK Tweten, MW Parker

Structure | Published : 2012

DOI: 10.1016/j.str.2011.11.017

Abstract

The cholesterol-dependent cytolysins (CDCs) punch holes in target cell membranes through a highly regulated process. Streptococcus mitis lectinolysin (LLY) exhibits another layer of regulation with a lectin domain that enhances the pore-forming activity of the toxin. We have determined the crystal structures of the lectin domain by itself and in complex with various glycans that reveal the molecular basis for the Lewis antigen specificity of LLY. A small-angle X-ray scattering study of intact LLY reveals the molecule is flat and elongated with the lectin domain oriented so that the Lewis antigen-binding site is exposed. We suggest that the lectin domain enhances the pore-forming activity of ..

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University of Melbourne Researchers

Terry Mulhern Author

Michael Parker Author

Grants

Awarded by National Institutes of Health

Funding Acknowledgements

This research was partly undertaken on the MX1 and SAXS/WAXS beamlines at the Australian Synchrotron, Victoria, Australia. We thank Dr. Julian Adams and the other beamline staff for their assistance. We also thank David Ascher for help with mass spectrometry and Dr. Paul Rams land for expert comments on our manuscript. We thank Dr. Mike Kuiper for his help in the preparation of the graphical abstract. This work was partly carried out in the Australian Cancer Research Foundation Rational Drug Discovery Facility. This work was also supported by a grant from the National Health and Medical Research Council of Australia (NHMRC) to M.W.P. and funding from the Victorian Government Operational Infrastructure Support Scheme to St Vincent's Institute. R.K.T. received support from Grant AI037657 from the National Institutes of Health. S.C.F. was supported by a NHMRC Industry Fellowship. M.W.P. is an Australian Research Council Federation Fellow and NHMRC Honorary Fellow.