Asset Details
Do you wish to reserve the book?
The PfRCR complex bridges malaria parasite and erythrocyte during invasion
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
The PfRCR complex bridges malaria parasite and erythrocyte during invasion
Do you wish to request the book?
The PfRCR complex bridges malaria parasite and erythrocyte during invasion
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
The PfRCR complex bridges malaria parasite and erythrocyte during invasion
2024
Overview
The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex
1
, containing PfRH5 (refs.
2
,
3
), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite,
Plasmodium falciparum
. Invasion can be prevented by antibodies
3
–
6
or nanobodies
1
against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex
7
,
8
, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane
9
, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies
5
neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies
6
, binds to the PfCSS–PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.
Structural studies show how the PfRCR complex of
Plasmodium falciparum
forms a bridge between erythrocyte and parasite membranes, and how PfCyRPA-binding antibodies neutralize invasion through a steric mechanism, opening the way to new approaches in rational vaccine design.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/31
/ 14/63
/ 82/103
/ Animals
/ Antibodies, Neutralizing - immunology
/ Antigens, Protozoan - chemistry
/ Antigens, Protozoan - immunology
/ Binding
/ Blood
/ Humanities and Social Sciences
/ Humans
/ Malaria
/ Malaria Vaccines - immunology
/ Malaria, Falciparum - immunology
/ Malaria, Falciparum - metabolism
/ Malaria, Falciparum - parasitology
/ Malaria, Falciparum - pathology
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - immunology
/ Multiprotein Complexes - metabolism
/ Multiprotein Complexes - ultrastructure
/ Plasmodium falciparum - metabolism
/ Plasmodium falciparum - pathogenicity
/ Proteins
/ Protozoan Proteins - chemistry
/ Protozoan Proteins - immunology
/ Protozoan Proteins - metabolism
/ Protozoan Proteins - ultrastructure
/ Science
/ Tails
/ Vaccines
