PDBsum entry 6mpv

Cell invasion

PDB id: 6mpv

Contents

Protein chains

315 a.a.

276 a.a.

16 a.a.

Ligands

UNK-UNK-UNK-UNK-UNK

PDB id:

6mpv

Name:

Cell invasion

Title:

Cryo-electron microscopy structure of plasmodium falciparum rh5/cyrpa/ripr invasion complex

Structure:

Cysteine-rich protective antigen. Chain: a. Engineered: yes. Reticulocyte binding protein 5. Chain: b. Engineered: yes. Pfripr. Chain: c. Engineered: yes.

Source:

Plasmodium falciparum (isolate 3d7). Organism_taxid: 36329. Strain: isolate 3d7. Gene: pf3d7_0423800. Expressed in: insect cell expression vector ptie1. Expression_system_taxid: 266783. Plasmodium falciparum. Organism_taxid: 5833. Plasmodium falciparum 3d7.

Authors:

W.Wilson,Y.Zhiheng,A.F.Cowman

Key ref:

W.Wong et al. (2019). Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex. Nature, 565, 118-121. PubMed id: 30542156 DOI: 10.1038/s41586-018-0779-6

Date:

08-Oct-18 Release date: 12-Dec-18

Protein chain

Q8IFM8  (Q8IFM8_PLAF7) -  Cysteine-rich protective antigen from Plasmodium falciparum (isolate 3D7)

Seq: 362 a.a.

Struc: 315 a.a.*

Protein chain

B2L3N7  (B2L3N7_PLAFA) -  Reticulocyte binding protein 5 from Plasmodium falciparum

Seq: 526 a.a.

Struc: 276 a.a.*

Protein chain

No UniProt id for this chain

Struc: 16 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/s41586-018-0779-6

Nature 565:118-121 (2019)

PubMed id: 30542156

Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex.

W.Wong, R.Huang, S.Menant, C.Hong, J.J.Sandow, R.W.Birkinshaw, J.Healer, A.N.Hodder, U.Kanjee, C.J.Tonkin, D.Heckmann, V.Soroka, T.M.M.Søgaard, T.Jørgensen, M.T.Duraisingh, P.E.Czabotar, W.A.de Jongh, W.H.Tham, A.I.Webb, Z.Yu, A.F.Cowman.

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 basigin^1,2, 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.