title: Widespread functional specialization of Plasmodium falciparum erythrocyte membrane protein 1 family members to bind CD36 analysed across a parasite genome.
abstract: Plasmodium falciparum-infected erythrocytes sequester from blood circulation by binding host endothelium. A large family of variant proteins mediates cytoadherence and their binding specificity determines parasite sequestration patterns and potential for disease. The aim of the present study was to understand how binding properties are encoded into family members and to develop sequence algorithms for predicting binding. To accomplish these goals computational approaches and a binding assay were used to characterize adhesion across Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins in the 3D7 parasite genome. We report that most family members encode the capacity to bind CD36 in the protein's semi-conserved head structure and describe the sequence characteristics of a group of PfEMP1 proteins that do not. Structural and functional grouping of PfEMP1 proteins based upon head structure and additional domain architectural properties provide new insights into the protein family. These can be used to investigate the role of proteins in malaria pathogenesis and potentially tailor vaccines to recognize particular binding variants.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80525, USA.
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Robinson
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Welch
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Smith
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D004912:Erythrocytes / Q000469:parasitology; D017125:Genes, Protozoan; D016678:Genome; D006801:Humans; D017780:Malaria Vaccines; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D018955:CD36 Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum