Journal article
Cryo-EM structure of an essential Plasmodium vivax invasion complex
J Gruszczyk, RK Huang, LJ Chan, S Menant, C Hong, JM Murphy, YF Mok, MDW Griffin, RD Pearson, W Wong, AF Cowman, Z Yu, WH Tham
Nature | NATURE PUBLISHING GROUP | Published : 2018
Abstract
Plasmodium vivax is the most widely distributed malaria parasite that infects humans 1 . P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. vivax reticulocyte-binding protein 2b (PvRBP2b) and transferrin receptor 1 (TfR1) 2 . TfR1-deficient erythroid cells are refractory to invasion by P. vivax, and anti-PvRBP2b monoclonal antibodies inhibit reticulocyte binding and block P. vivax invasion in field isolates 2 . Here we report a high-resolution cryo-electron microscopy structure of a ternary complex of PvRBP2b bound to human TfR1 and transferrin, at 3.7 Å resolution. Mutational analyses show that PvRBP2b residues involved in comple..
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Awarded by Australian Research Council
Funding Acknowledgements
We thank J. Newman from CSIRO Collaborative Crystallization Centre for assistance with setting up the crystallization screens, the Walter and Eliza Hall Institute's Monoclonal Antibody Facility for production of antibodies, and the MX and SAXS beamline staff at the Australian Synchrotron for their assistance during data collection. This work was supported in part by the Australian Research Council Future Fellowship to W.-H.T. and M.D.W.G., a Speedy Innovation Grant to W.-H.T. and a National Health and Medical Research Council fellowship (1105754) to J.M.M. W.-H.T. is a Howard Hughes Medical Institute-Wellcome Trust International Research Scholar (208693/Z/17/Z). R.D.P. is funded by Wellcome Trust (090770). The authors acknowledge support from the Drakensberg Trust, the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.