title: A family of erythrocyte binding proteins of malaria parasites.
abstract: Malaria erythrocyte binding proteins use the Duffy blood group antigen (Plasmodium vivax and Plasmodium knowlesi) and sialic acid (Plasmodium falciparum) on the erythrocyte surface as receptors. We had previously cloned the one P. vivax gene, the one P. falciparum gene, and part of one of the three P. knowlesi genes encoding these erythrocyte binding proteins and described the homology between the P. knowlesi and P. vivax genes. We have completed the cloning and sequencing of the three P. knowlesi genes and identified introns in the P. vivax and P. falciparum genes that correct the previously published deduced amino acid sequences. All have similar structures, with one or two exons encoding the signal sequence and the erythrocyte binding domain, an exon encoding the transmembrane domain, and two exons encoding the cytoplasmic domain with the exception of the P. knowlesi beta gene. The regions of amino acid sequence homology among all the genes are the 5' and 3' cysteine-rich regions of the erythrocyte binding domain. On the basis of gene structure and amino acid homology, we propose that the Duffy binding proteins and the sialic acid binding protein are members of a gene family. The level of conservation (approximately 70%) of the deduced amino acid sequences in the 5' cysteine-rich region between the P. vivax protein and the three P. knowlesi proteins is as great as between the three P. knowlesi proteins themselves; the P. knowlesi beta protein just 3' to this cysteine-rich region is homologous to the P. vivax protein but not to the other P. knowlesi proteins. Conservation of amino acid sequences among these organisms, separated in evolution, may indicate the regions where the adhesin function resides.
authors.affiliation: Laboratory of Malaria Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: J H
authors.initials: JH
authors.lastname: Adams
authors.forename: B K
authors.initials: BK
authors.lastname: Sim
authors.forename: S A
authors.initials: SA
authors.lastname: Dolan
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.forename: D C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: L H
authors.initials: LH
authors.lastname: Miller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D003545:Cysteine; D016054:DNA, Protozoan / Q000235:genetics* / Q000302:isolation & purification; D004375:Duffy Blood-Group System / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology; D005091:Exons; D015723:Gene Library; D008253:Macaca mulatta; D008288:Malaria / Q000469:parasitology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009838:Oligodeoxyribonucleotides; D010963:Plasmodium falciparum / Q000235:genetics*; D016790:Plasmodium knowlesi / Q000235:genetics*; D010966:Plasmodium vivax / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; D016054:DNA, Protozoan; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D009838:Oligodeoxyribonucleotides; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D003545:Cysteine