title: Plasmodium falciparum BAEBL binds to heparan sulfate proteoglycans on the human erythrocyte surface.
abstract: Erythrocyte invasion is critical to the pathogenesis and survival of the malarial parasite, Plasmodium falciparum. This process is partly mediated by proteins that belong to the Duffy binding-like family, which are expressed on the merozoite surface. One of these proteins, BAEBL (also known as EBA-140), is thought to bind to glycophorin C in a sialic acid-dependent manner. In this report, by the binding assay between recombinant BAEBL protein and enzyme-treated erythrocytes, we show that the binding of BAEBL to erythrocytes is mediated primarily by sialic acid and partially through heparan sulfate (HS). Because BAEBL binds to several kinds of HS proteoglycans or purified HS, the BAEBL-HS binding was found to be independent of the HS proteoglycan peptide backbone and the presence of sialic acid moieties. Furthermore, both the sialic acid- and HS-dependent binding were disrupted by the addition of soluble heparin. This inhibition may be the result of binding between BAEBL and heparin. Invasion assays demonstrated that HS-dependent binding was related to the efficiency of merozoite invasion. These results suggest that HS functions as a factor that promotes the binding of BAEBL and merozoite invasion. Moreover, these findings may explain the invasion inhibition mechanisms observed following the addition of heparin and other sulfated glycoconjugates.
authors: Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors: Kyousuke
authors: K
authors: Kobayashi
authors: Kentaro
authors: K
authors: Kato
authors: Tatsuki
authors: T
authors: Sugi
authors: Hitoshi
authors: H
authors: Takemae
authors: Kishor
authors: K
authors: Pandey
authors: Haiyan
authors: H
authors: Gong
authors: Yukinobu
authors: Y
authors: Tohya
authors: Hiroomi
authors: H
authors: Akashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins; D052940:Merozoites / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D018692:Antimanic Agents; D002352:Carrier Proteins; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C451423:erythrocyte binding protein-2, Plasmodium falciparum; D006493:Heparin; D019158:N-Acetylneuraminic Acid