8CDD

PfRH5-PfCyRPA-PfRIPR complex from Plasmodium falciparum bound to antibody Cy.003

8CDD の概要

• エントリーDOI: 10.2210/pdb8cdd/pdb
• EMDBエントリー: 16569 16640
• 分子名称: Rh5-interacting protein, Cysteine-rich protective antigen, Reticulocyte-binding protein homolog 5, ... (5 entities in total)
• 機能のキーワード: plasmodium falciparum, erythrocyte-invasion, pfrcr, blood stage malaria vaccine, cell adhesion
• 由来する生物種: Plasmodium falciparum 3D7; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 270062.40

構造登録者

Farrell, B.,Higgins, M.K. (登録日: 2023-01-30, 公開日: 2023-10-25, 最終更新日: 2025-07-09)

主引用文献

Farrell, B.,Alam, N.,Hart, M.N.,Jamwal, A.,Ragotte, R.J.,Walters-Morgan, H.,Draper, S.J.,Knuepfer, E.,Higgins, M.K.
The PfRCR complex bridges malaria parasite and erythrocyte during invasion.
Nature, 625:578-584, 2024

PubMed Abstract: The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5 (refs. ), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies or nanobodies 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, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane, 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 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, 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.

PubMed: 38123677
DOI: 10.1038/s41586-023-06856-1

実験手法

ELECTRON MICROSCOPY (3 Å)