Ulf Skoglund
Okinawa Institute of Science and Technology, Japan
Title: Structure of Human IgM in complex with the Malaria protein PfEMP1
Biography
Biography: Ulf Skoglund
Abstract
Children under the age of 5 years have huge malaria burden in endemic area. Increased death in complicated malaria is due to increased sequestration to tissues and agglutination with erythrocytes and cells of our immune system. It is known that parasites that bind to non-immune IgM cause severe malaria due to increased rosetting (agglutination). Using biochemical, parasitology and electron tomography techniques we have identified that
PfEMP1, a crescent shaped molecule interacts with human IgM through its bulky C-terminus (membrane proximal) in 1:1 and 2:1 ratio. While the bulky C terminus limits the stoichiometry of this interaction yet clusters parasite molecule PfEMP1 (P. falciparum Erythrocyte Membrane Protein-1) to mediate robust host parasite interaction. Structural analysis revealed that PfEMP1 could also preclude the activation of complement mediated lysis of parasite in spite of IgM deposition on parasitized RBC surface. We also found that IgM although not a rosetting factor enhances this interaction by increasing the strength of this interaction by at least four fold. In terms of physiological relevance, we need to understand that new born babies have high level of IgM and could be more prone to agglutination and hence more deaths due to malaria.