title: A novel erythrocyte binding antigen-175 paralogue from Plasmodium falciparum defines a new trypsin-resistant receptor on human erythrocytes.
abstract: The recognition and invasion of human erythrocytes by the most lethal malaria parasite Plasmodium falciparum is dependent on multiple ligand-receptor interactions. Members of the erythrocyte binding-like (ebl) family, including the erythrocyte binding antigen-175 (EBA-175), are responsible for high affinity binding to glycoproteins on the surface of the erythrocyte. Here we describe a paralogue of EBA-175 and show that this protein (EBA-181/JESEBL) binds in a sialic acid-dependent manner to erythrocytes. EBA-181 is expressed at the same time as EBA-175 and co-localizes with this protein in the microneme organelles of asexual stage parasites. The receptor binding specificity of EBA-181 to erythrocytes differs from other members of the ebl family and is trypsin-resistant and chymotrypsin-sensitive. Furthermore, using glycophorin B-deficient erythrocytes we show that binding of EBA-181 is not dependent on this sialoglycoprotein. The level of expression of EBA-181 differs among parasite lines, and the importance of this ligand for invasion appears to be strain-dependent as the EBA-181 gene can be disrupted in W2mef parasites, without affecting the invasion phenotype, but cannot be targeted in 3D7 parasites.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.
authors.forename: Tim-Wolf
authors.initials: TW
authors.lastname: Gilberger
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Thompson
authors.forename: Tony
authors.initials: T
authors.lastname: Triglia
authors.forename: Robert T
authors.initials: RT
authors.lastname: Good
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000378:metabolism*; D000954:Antigens, Surface; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002918:Chymotrypsin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D011995:Recombination, Genetic; D012795:Sialoglycoproteins / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology*
chemical_list: D000941:Antigens; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D002352:Carrier Proteins; C474029:EBA-181 protein, Plasmodium falciparum; D008024:Ligands; D015800:Protozoan Proteins; D012795:Sialoglycoproteins; C065668:erythrocyte-binding antigen 175, Plasmodium; D002918:Chymotrypsin; D014357:Trypsin