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Blood. 2015 Apr 23;125(17):2704-11. doi: 10.1182/blood-2014-11-611707. Epub 2015 Mar 16.

Merozoite surface protein 1 recognition of host glycophorin A mediates malaria parasite invasion of red blood cells.

Author information

1
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;
2
Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; and Department of Medicine, St. Elizabeth's Medical Center, and.
3
Department of Developmental, Molecular & Chemical Biology, Tufts University School of Medicine, Boston, MA;
4
Department of Medicine, St. Elizabeth's Medical Center, and.
5
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.

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.

PMID:
25778531
PMCID:
PMC4408295
DOI:
10.1182/blood-2014-11-611707
[Indexed for MEDLINE]
Free PMC Article

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