title: Merozoite surface protein 1 recognition of host glycophorin A mediates malaria parasite invasion of red blood cells.
abstract: Plasmodium falciparum invasion of human red blood cells (RBCs) is an intricate process requiring a number of distinct ligand-receptor interactions at the merozoite-erythrocyte interface. Merozoite surface protein 1 (MSP1), a highly abundant ligand coating the merozoite surface in all species of malaria parasites, is essential for RBC invasion and considered a leading candidate for inclusion in a multiple-subunit vaccine against malaria. Our previous studies identified an interaction between the carboxyl-terminus of MSP1 and RBC band 3. Here, by employing phage display technology, we report a novel interaction between the amino-terminus of MSP1 and RBC glycophorin A (GPA). Mapping of the binding domains established a direct interaction between malaria MSP1 and human GPA within a region of MSP1 known to potently inhibit P falciparum invasion of human RBCs. Furthermore, a genetically modified mouse model lacking the GPA- band 3 complex in RBCs is completely resistant to malaria infection in vivo. These findings suggest an essential role of the MSP1-GPA-band 3 complex during the initial adhesion phase of malaria parasite invasion of RBCs.
authors.affiliation: Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, and Department of Developmental, Molecular & Chemical Biology, Tufts University School of Medicine, Boston, MA;
authors.forename: Michael R
authors.initials: MR
authors.lastname: Baldwin
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; and Department of Medicine, St. Elizabeth's Medical Center, and.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Developmental, Molecular & Chemical Biology, Tufts University School of Medicine, Boston, MA;
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hanada
authors.affiliation: Department of Medicine, St. Elizabeth's Medical Center, and.
authors.forename: Shih-Chun
authors.initials: SC
authors.lastname: Liu
authors.affiliation: Department of Developmental, Molecular & Chemical Biology, Tufts University School of Medicine, Boston, MA; Programs in Cellular and Molecular Physiology, Pharmacology, and Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA.
authors.forename: Athar H
authors.initials: AH
authors.lastname: Chishti
mesh_terms: D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D017353:Gene Deletion; D006021:Glycophorins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D006021:Glycophorins; D020066:Merozoite Surface Protein 1