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
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:565:y:2019:i:7737:d:10.1038_s41586-018-0779-6. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.