Plasmodium falciparum virulence is associated with sequestration of infected erythrocytes. Microvascular binding mediated by PfEMP1 in complex with non-immune immunoglobulin M (IgM) is common among ...Plasmodium falciparum virulence is associated with sequestration of infected erythrocytes. Microvascular binding mediated by PfEMP1 in complex with non-immune immunoglobulin M (IgM) is common among parasites that cause both severe childhood malaria and pregnancy-associated malaria. Here, we present cryo-molecular electron tomography structures of human IgM, PfEMP1 and their complex. Three-dimensional reconstructions of IgM reveal that it has a dome-like core, randomly oriented Fab2s units, and the overall shape of a turtle. PfEMP1 is a C- shaped molecule with a flexible N terminus followed by an arc-shaped backbone and a bulky C terminus that interacts with IgM. Our data demonstrate that the PfEMP1 binding pockets on IgM overlap with those of C1q, and the bulkiness of PfEMP1 limits the capacity of IgM to interact with PfEMP1. We suggest that P. falciparum exploits IgM to cluster PfEMP1 into an organized matrix to augment its affinity to host cell receptors.
EMDB-2882: Cryo-Molecular electron tomography of NTS-DBL1alphaCIDRgamma (N-terminal domain of PfEMP1-IT4Var60) Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2883: Cryo-Molecular electron tomography of NTS-DBL1alphaCIDRgamma (N-terminal domain of PfEMP1-IT4Var60) Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2884: Cryo-Molecular electron tomography of PfEMP1-IT4Var60) Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2885: Cryo-Molecular electron tomography of PfEMP1-IT4Var60) Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2886: Cryo-Molecular electron tomography of PfEMP1-IT4Var60) Method: EM (subtomogram averaging) / Resolution: 20.0 Å
EMDB-2887: Cryo-Molecular electron tomography of human non-immune soluble pentameric IgM Method: EM (tomography) / Resolution: 25.0 Å
EMDB-2888: Cryo-Molecular electron tomography of human non-immune soluble pentameric IgM Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2889: Cryo-Molecular electron tomography of human non-immune soluble pentameric IgM Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2890: Cryo-Molecular electron tomography of human non-immune soluble pentameric IgM Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2891: Cryo-Molecular electron tomography of complex of human non-immune soluble pentameric IgM and PfEMP1-IT4Var60 in 1:1 ratio Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2892: Cryo-Molecular electron tomography of complex of human non-immune soluble pentameric IgM and PfEMP1-IT4Var60 in 1:1 ratio Method: EM (tomography) / Resolution: 20.0 Å
EMDB-2893: Cryo-Molecular electron tomography of complex of human non-immune soluble pentameric IgM and PfEMP1-IT4Var60 in 1:1 ratio Method: EM (tomography) / Resolution: 25.0 Å
EMDB-2894: Cryo-Molecular electron tomography of complex of human non-immune soluble pentameric IgM and PfEMP1-IT4Var60 in 1:2 ratio Method: EM (tomography) / Resolution: 25.0 Å
EMDB-2895: Cryo-Molecular electron tomography of complex of human non-immune soluble pentameric IgM and PfEMP1-IT4Var60 in 1:2 ratio Method: EM (tomography) / Resolution: 20.0 Å
EMDB-6554: Cryo-Molecular electron tomography of IgM Method: EM (tomography) / Resolution: 25.0 Å
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Plasmodium falciparum (malaria parasite P. falciparum)
Homo sapiens (human)
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Plasmodium falciparum (malaria parasite P. falciparum)
