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TitleArchitecture of Human IgM in Complex with P. falciparum Erythrocyte Membrane Protein 1.
Journal, issue, pagesCell Rep, Vol. 14, Issue 4, Page 723-736, Year 2016
Publish dateFeb 2, 2016
AuthorsReetesh Raj Akhouri / Suchi Goel / Hirotoshi Furusho / Ulf Skoglund / Mats Wahlgren /
PubMed AbstractPlasmodium 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.
External linksCell Rep / PubMed:26776517
MethodsEM (tomography) / EM (subtomogram averaging)
Resolution20.0 - 25.0 Å
Structure data

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

Source
  • Plasmodium falciparum (malaria parasite P. falciparum)
  • Homo sapiens (human)

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