Journal article
Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins
SL Lawrence, MA Gorman, SC Feil, TD Mulhern, MJ Kuiper, AJ Ratner, RK Tweten, CJ Morton, MW Parker
Structure | CELL PRESS | Published : 2016
Abstract
Cholesterol-dependent cytolysins (CDCs) are a family of pore-forming toxins that punch holes in the outer membrane of eukaryotic cells. Cholesterol serves as the receptor, but a subclass of CDCs first binds to human CD59. Here we describe the crystal structures of vaginolysin and intermedilysin complexed to CD59. These studies, together with small-angle X-ray scattering, reveal that CD59 binds to each at different, though overlapping, sites, consistent with molecular dynamics simulations and binding studies. The CDC consensus undecapeptide motif, which for the CD59-responsive CDCs has a proline instead of a tryptophan in the motif, adopts a strikingly different conformation between the struc..
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Awarded by Australian Government
Funding Acknowledgements
This research was partly undertaken on the MX2 and SAXS/WAXS beamlines at the Australian Synchrotron (Clayton, Victoria), and we thank the beamline staff for their assistance. This work was supported by an Australian Research Council Discovery Grant DP160101874 to M.W.P. MD simulations were supported by a grant from the Victorian Life Sciences Computation Initiative number VR0021 on its Peak Computing Facility (University of Melbourne), an initiative of the Victorian Government and by resources provided by the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia. This work was also supported by NIH grant AI037657 to R.K.T. Funding from the Victorian Government Operational Infrastructure Support Scheme to St Vincent's Institute is acknowledged. M.W.P. is a National Health and Medical Research Council of Australia Research Fellow.