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Structure of Plasmodium falciparum Rh5–CyRPA–Ripr invasion complex

Author

Listed:
  • Wilson Wong

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Rick Huang

    (Howard Hughes Medical Institute)

  • Sebastien Menant

    (Walter and Eliza Hall Institute of Medical Research)

  • Chuan Hong

    (Howard Hughes Medical Institute)

  • Jarrod J. Sandow

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Richard W. Birkinshaw

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Julie Healer

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Anthony N. Hodder

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Usheer Kanjee

    (Harvard T. H. Chan School of Public Health)

  • Christopher J. Tonkin

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Denise Heckmann

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Vladislav Soroka

    (ExpreS2ion Biotechnologies)

  • Teit Max Moscote Søgaard

    (ExpreS2ion Biotechnologies)

  • Thomas Jørgensen

    (ExpreS2ion Biotechnologies)

  • Manoj T. Duraisingh

    (Harvard T. H. Chan School of Public Health)

  • Peter E. Czabotar

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Willem A. Jongh

    (ExpreS2ion Biotechnologies)

  • Wai-Hong Tham

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Andrew I. Webb

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Zhiheng Yu

    (Howard Hughes Medical Institute)

  • Alan F. Cowman

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

Abstract

Plasmodium falciparum causes the severe form of malaria that has high levels of mortality in humans. Blood-stage merozoites of P. falciparum invade erythrocytes, and this requires interactions between multiple ligands from the parasite and receptors in hosts. These interactions include the binding of the Rh5–CyRPA–Ripr complex with the erythrocyte receptor basigin1,2, which is an essential step for entry into human erythrocytes. Here we show that the Rh5–CyRPA–Ripr complex binds the erythrocyte cell line JK-1 significantly better than does Rh5 alone, and that this binding occurs through the insertion of Rh5 and Ripr into host membranes as a complex with high molecular weight. We report a cryo-electron microscopy structure of the Rh5–CyRPA–Ripr complex at subnanometre resolution, which reveals the organization of this essential invasion complex and the mode of interactions between members of the complex, and shows that CyRPA is a critical mediator of complex assembly. Our structure identifies blades 4–6 of the β-propeller of CyRPA as contact sites for Rh5 and Ripr. The limited contacts between Rh5–CyRPA and CyRPA–Ripr are consistent with the dissociation of Rh5 and Ripr from CyRPA for membrane insertion. A comparision of the crystal structure of Rh5–basigin with the cryo-electron microscopy structure of Rh5–CyRPA–Ripr suggests that Rh5 and Ripr are positioned parallel to the erythrocyte membrane before membrane insertion. This provides information on the function of this complex, and thereby provides insights into invasion by P. falciparum.

Suggested Citation

  • Wilson Wong & Rick Huang & Sebastien Menant & Chuan Hong & Jarrod J. Sandow & Richard W. Birkinshaw & Julie Healer & Anthony N. Hodder & Usheer Kanjee & Christopher J. Tonkin & Denise Heckmann & Vladi, 2019. "Structure of Plasmodium falciparum Rh5–CyRPA–Ripr invasion complex," Nature, Nature, vol. 565(7737), pages 118-121, January.
  • Handle: RePEc:nat:nature:v:565:y:2019:i:7737:d:10.1038_s41586-018-0779-6
    DOI: 10.1038/s41586-018-0779-6
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    Cited by:

    1. Tony Triglia & Stephen W. Scally & Benjamin A. Seager & Michał Pasternak & Laura F. Dagley & Alan F. Cowman, 2023. "Plasmepsin X activates the PCRCR complex of Plasmodium falciparum by processing PfRh5 for erythrocyte invasion," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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