A Family of Erythrocyte Binding Proteins of Malaria Parasites

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-08, Vol.89 (15), p.7085-7089
• Main Authors: Adams, John H., B. Kim Lee Sim, Dolan, Stephen A., Fang, Xiangdong, Kaslow, David C., Miller, Louis H.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antigens, Protozoan; Base Sequence; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; Carrier proteins; Carrier Proteins - genetics; cDNA; Classification; Cloning, Molecular; Complementary DNA; Cysteine; DNA, Protozoan - genetics; DNA, Protozoan - isolation & purification; Duffy Blood-Group System - genetics; Erythrocytes; Erythrocytes - parasitology; Exons; Fundamental and applied biological sciences. Psychology; Gene Library; genes; Genetics; Genomics; Introns; Macaca mulatta; Malaria; Malaria - parasitology; Molecular Sequence Data; Multigene Family; nucleotide sequence; Oligodeoxyribonucleotides; Open reading frames; Parasites; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium knowlesi; Plasmodium knowlesi - genetics; Plasmodium vivax; Plasmodium vivax - genetics; predictions; Proteins; Protozoa; Protozoan Proteins - genetics; Receptors, Cell Surface; Regional identity; Sequence Homology, Nucleic Acid; sialic acid-binding protein
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.15.7085

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 β 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 (≈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 β 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.