4U0Q

Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) bound to basigin

Summary for 4U0Q

• Entry DOI: 10.2210/pdb4u0q/pdb
• Descriptor: Reticulocyte binding protein 5, Basigin (2 entities in total)
• Functional Keywords: malaria erythrocyte invasion, signaling protein
• Biological source: Plasmodium falciparum; More
• Cellular location: Cell membrane ; Single-pass type I membrane protein : P35613
• Total number of polymer chains: 4
• Total formula weight: 184767.51

Authors

Wright, K.E.,Hjerrild, K.A.,Bartlett, J.,Douglas, A.D.,Jin, J.,Brown, R.E.,Ashfield, R.,Clemmensen, S.B.,de Jongh, W.A.,Draper, S.J.,Higgins, M.K. (deposition date: 2014-07-14, release date: 2014-08-13, Last modification date: 2024-10-23)

Primary citation

Wright, K.E.,Hjerrild, K.A.,Bartlett, J.,Douglas, A.D.,Jin, J.,Brown, R.E.,Illingworth, J.J.,Ashfield, R.,Clemmensen, S.B.,de Jongh, W.A.,Draper, S.J.,Higgins, M.K.
Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies.
Nature, 515:427-430, 2014

PubMed Abstract: Invasion of host erythrocytes is essential to the life cycle of Plasmodium parasites and development of the pathology of malaria. The stages of erythrocyte invasion, including initial contact, apical reorientation, junction formation, and active invagination, are directed by coordinated release of specialized apical organelles and their parasite protein contents. Among these proteins, and central to invasion by all species, are two parasite protein families, the reticulocyte-binding protein homologue (RH) and erythrocyte-binding like proteins, which mediate host-parasite interactions. RH5 from Plasmodium falciparum (PfRH5) is the only member of either family demonstrated to be necessary for erythrocyte invasion in all tested strains, through its interaction with the erythrocyte surface protein basigin (also known as CD147 and EMMPRIN). Antibodies targeting PfRH5 or basigin efficiently block parasite invasion in vitro, making PfRH5 an excellent vaccine candidate. Here we present crystal structures of PfRH5 in complex with basigin and two distinct inhibitory antibodies. PfRH5 adopts a novel fold in which two three-helical bundles come together in a kite-like architecture, presenting binding sites for basigin and inhibitory antibodies at one tip. This provides the first structural insight into erythrocyte binding by the Plasmodium RH protein family and identifies novel inhibitory epitopes to guide design of a new generation of vaccines against the blood-stage parasite.

PubMed: 25132548
DOI: 10.1038/nature13715

Experimental method

X-RAY DIFFRACTION (3.1 Å)