title: Polymorphism in a Plasmodium falciparum erythrocyte-binding ligand changes its receptor specificity.
abstract: Recognition of human erythrocytes by Plasmodium species depends in part on Region II of the Duffy binding-like family of parasite ligands, which includes BA erythrocyte binding ligand (BAEBL) of P. falciparum. In previous studies of BAEBL from two clones, Dd2/Nm from Vietnam and E12 from Papua New Guinea (PNG), it was found that BAEBL bound different erythrocyte receptors. Because of variation in binding specificity, we studied the sequence and erythrocyte binding specificity of Region II of BAEBL in P. falciparum clones from different parts of the world. We observed five nucleotide substitutions leading to five amino acid changes and five polymorphisms in Region II of BAEBL in parasites from both PNG and other parts of the world. We expressed four of the polymorphisms on COS cells and determined their binding to enzyme-treated erythrocytes and to Gerbich-negative erythrocytes. We also performed erythrocyte-binding assay using the native protein from radiolabeled culture supernatant. Both assays demonstrated that each of the four polymorphisms in the parasite ligand, BAEBL, bound to a different receptor on erythrocytes. These results suggest that P. falciparum has evolved multiple invasion pathways dependent on polymorphisms in the BAEBL ligand.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive, Building 4 Room B1-41, Bethesda, MD 20892, USA.
authors.forename: D C Ghislaine
authors.initials: DC
authors.lastname: Mayer
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Mu
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Feng
authors.forename: Xin-zhuan
authors.initials: XZ
authors.lastname: Su
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010219:Papua New Guinea; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D015800:Protozoan Proteins; C451423:erythrocyte binding protein-2, Plasmodium falciparum