Understanding how RH5 interacts with basigin and inhibitory antibodies

How does the malaria parasite get inside human red blood cells?

The symptoms of malaria occur when Plasmodium parasites invade and divide within human blood cells. If we can stop red blood cell invasion, we can prevent the symptoms of the disease and the transmission of the parasite.

Molecules of the RH-protein family play important roles in the invasion process, mediating interactions between the parasite and receptors on the surfaces of red blood cells. For the parasite that causes the most deadly form of human malaria, Plasmodium falciparum, the most critical RH-protein is RH5, which makes an essential interaction with the human receptor basigin.

Kate Wright was able to use protein crystallography to determine the structure of RH5 bound to basigin. This first structure of an RH protein revealed its novel kite-like architecture and identified the basigin-binding site at its tip.

Simon Draper’s group had obtained a panel of mouse monoclonal antibodies that target RH5 and had identified which were able to prevent the parasite from invading red blood cells. Kate was also able to structurally characterise the epitopes of two of these inhibitory antibodies, showing that they bind in the region of the basigin binding site.

The study gave the first view of a critical interaction in the development of malaria and provides insight to guide the design of novel vaccines.

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.* and Higgins M.K.* (2014) Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies. Nature 515 427-30 (* joint corresponding).