Glycophorin C is the receptor for the Plasmodium falciparum erythrocyte binding ligand PfEBP-2 (baebl)

Lobo, Cheryl-Ann; Rodriguez, Marilis; Reid, Marion E.; Lustigman, Sara

doi:10.1182/blood-2002-10-3076

Cited by 153 publications

(154 citation statements)

References 26 publications

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…Contrary to our results, Lobo et al (10) concluded that glycophorin C was the ligand for BAEBL variant (INKK) based on the observation that INKK did not bind to Leach erythrocytes that lack glycophorin C or to Yus erythrocytes that have a deletion of exon 2 of glycophorin C. It was also observed in the previous study that antibodies to glycophorin C partially inhibited the binding of INKK to erythrocytes (10). However, these results are not entirely conclusive because binding to Leach and Yus erythrocytes was performed with erythrocytes frozen as pellets in liquid nitrogen that may have been unsuitable for the binding assay.…”

Section: Binding Of Baebl (Vstk) To Erythrocytes Is Inhibited By Glyccontrasting

confidence: 56%

The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL

Mayer

Jiang

Achur

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Plasmodium vivax uses a single member of the Duffy binding-like (DBL) receptor family to invade erythrocytes and is not found inWest Africa where its erythrocyte ligand, the Duffy blood group antigen, is missing. In contrast, Plasmodium falciparum expresses four members of the DBL family, and remarkably, single-point mutations of two of these receptors (BAEBL and JESEBL) bind to entirely different erythrocyte ligands, greatly expanding the range of erythrocytes that P. falciparum can invade. In this article, we describe the molecular basis of the binding specificity for one BAEBL variant (VSTK) that binds to glycophorin C. We demonstrate that soluble glycophorin C completely blocks the binding of BAEBL (VSTK) to human erythrocytes, requiring 0.7 M for 50% inhibition, a concentration similar to that required by glycophorin A to block the binding of erythrocyte-binding antigen 175 to erythrocytes. BAEBL (VSTK) does not bind to Gerbich-negative erythrocytes that express a truncated form of glycophorin C because it lacks exon 3. The N-linked oligosaccharide of Gerbich-negative glycophorin C has a markedly different composition than the wild-type glycophorin C. Moreover, removal of the N-linked oligosaccharide from the wild-type glycophorin C eliminates its ability to inhibit binding of BAEBL (VSTK) to erythrocytes. These findings are consistent with the ligand for BAEBL (VSTK) being, in part, the N-linked oligosaccharide and suggest that single-point mutations in BAEBL allow P. falciparum to recognize oligosaccharides on different erythrocyte surface glycoproteins or glycolipids, greatly increasing its invasion range.mutations ͉ oligosaccharides ͉ DBL family R edundancy in erythrocyte invasion pathways is a critical factor in the survival of Plasmodium falciparum. Unlike Plasmodium vivax, which was eliminated from West Africa because of the absence of its erythrocyte ligand, the Duffy blood group antigen (1), there are no known mutations in erythrocyte surface proteins that lead to refractoriness to erythrocyte invasion by P. falciparum. The protein on the surface of P. vivax that binds the Duffy blood group antigen belongs to a family of genes in Plasmodium called the Duffy binding-like (DBL) family (2). P. falciparum expresses four DBL genes compared with a single gene in P. vivax, greatly expanding the potential receptor-ligand interactions for P. falciparum (2, 3). In addition, P. falciparum is able to recognize different erythrocyte ligands through singlepoint mutations in the receptor domain (region II) in two of its four DBL genes (BAEBL and JESEBL) (4, 5), further ensuring survival. Each clone of BAEBL is identified by four polymorphic amino acids in region II (4). One of the variants, BAEBL (VSTK), binds glycophorin C based on its inability to bind Gerbich-negative erythrocytes that lack exon 3 in glycophorin C (4, 6, 7). Because point mutations in BAEBL region II affect the receptor specificity for its ligand on erythrocytes, it is critical to determine the ligand recognized by BAEBL.Is it likely that the ...

show abstract

Section: Binding Of Baebl (Vstk) To Erythrocytes Is Inhibited By Glyccontrasting

confidence: 56%

The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL

Mayer

Jiang

Achur

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The receptor for one of the BAEBL variants is glycophorin C͞D, based on its inability to bind Gerbich-negative (15,16) and glycophorin C͞D-negative erythrocytes (17). On human erythrocytes carrying the Gerbich-negative blood group antigen, glycophorin C is missing part of its peptide backbone.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…These studies have revealed that distinct isolates of P. falciparum have varying abilities to use alternative invasion pathways, although many of the erythrocyte receptors are yet to be defined (9-13). On the erythrocyte side, several invasion pathways have been described involving the erythrocyte glycophorins, glycophorin A, and glycophorin C͞D, receptor X, receptor Y, and, potentially, glycolipids (8,(14)(15)(16)(17)(18)(19).The diversity of P. falciparum invasion pathways does not rely solely on the number of parasite ligands but also relies on polymorphisms in a single parasite ligand, BAEBL (EBA-140), each of which can recognize a different erythrocyte receptor (20). The polymorphic sites that we described in the F1 region of BAEBL by using our laboratory-maintained isolates were also found in field isolates from Ibadan, Nigeria (21).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Polymorphism in the Plasmodium falciparum erythrocyte-binding ligand JESEBL/EBA-181 alters its receptor specificity

Mayer

Kaneko

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

107

138

View full text Add to dashboard Cite

The malaria parasite lives within erythrocytes and depends on the binding of parasite ligands to host cell surface receptors for invasion. The most virulent human malaria parasite, Plasmodium falciparum, uses multiple ligands, including EBA-175, BAEBL, and JESEBL of the Duffy-binding-like (DBL) family of erythrocytebinding proteins, for invasion of human erythrocytes. Region II of these parasite ligands is the erythrocyte-binding domain. Previously, we had shown that polymorphism in region II of BAEBL leads to different erythrocyte-binding specificities. We have now identified and characterized the binding specificity of six JESEBL variants. We sequenced region II of JESEBL from 20 P. falciparum clones collected from various parts of the world where malaria is endemic. We observed eight JESEBL variants that contained amino acid polymorphisms at five positions among all clones. Seven of the eight variants could be connected by a single base change that led to an amino acid change. We investigated the functional significance of these polymorphisms by transiently expressing region II from six of JESEBL variants on the surface of Chinese hamster ovary cells. We observed four erythrocyte-binding patterns to enzymetreated erythrocytes. Thus, P. falciparum DBL ligands JESEBL and BAEBL can recognize multiple receptors on the erythrocyte surface. In contrast to Plasmodium vivax, which has disappeared from West Africa because of the Duffy-negative blood group, P. falciparum may have been successful in endemic areas because it has mutated the ligands of the DBL family to create multiple pathways of invasion, thus making selection of refractory erythrocytes unlikely.parasite polymorphism A ll of the clinical manifestations associated with human malaria infection are due to the asexual erythrocytic phase of the Plasmodium life cycle. Although the process by which the parasite enters erythrocytes is complex and not well understood, invasion of erythrocytes by Plasmodium can be divided into multiple steps. Initial attachment of the parasite to the erythrocyte is followed by reorientation to bring the apical end of the parasite into close contact with the surface of the erythrocyte (1). The parasite forms a junction between its apical end and the erythrocyte surface. Junction formation is irreversible and is followed by entry through invagination of the erythrocyte membrane (2). The process of junction formation is mediated by interaction between specific erythrocyte receptors and specific parasite ligands, as indicated by the inability of Plasmodium knowlesi, a simian malaria parasite that can infect humans, to form a junction with human erythrocytes lacking the Duffy blood group antigen and Plasmodium vivax to invade erythrocytes and infect Duffy-negative individuals (3-5).Unlike P. vivax, which is restricted to the erythrocytes expressing the Duffy blood group antigen and to reticulocytes, invasion of human erythrocytes by Plasmodium falciparum involves a number of apparently redundant receptor-ligand interactions between th...

show abstract

“…Plasmodium falciparum has a sophisticated invasion machinery with several EBL proteins that each bind a different erythrocyte receptor in a sialic acid-dependent manner (1). Erythrocyte-binding antigen 175 (PfEBA-175), erythrocyte-binding ligand 1 (PfEBL-1), and erythrocyte-binding antigen 140 (PfEBA-140) bind glycophorins A, B, and C, respectively (2)(3)(4). A fourth member of this family, erythrocyte-binding antigen 181 (PfEBA-181), binds an unknown receptor (5).…”

mentioning

confidence: 99%

Crystal and Solution Structures of Plasmodium falciparum Erythrocyte-binding Antigen 140 Reveal Determinants of Receptor Specificity during Erythrocyte Invasion

Lin¹,

Malpede²,

Batchelor

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The malaria parasite Plasmodium falciparum utilizes PfEBA-140 to invade host erythrocytes. Results: The minimal binding region of PfEBA-140 contains unique structural components compared with other Plasmodium invasion ligands. Conclusion: Distinct structural and mechanistic elements of PfEBA-140 binding are likely determinants of receptor specificity. Significance: This study provides the first view into the basis of receptor specificity of P. falciparum invasion ligands.

show abstract

Glycophorin C is the receptor for the Plasmodium falciparum erythrocyte binding ligand PfEBP-2 (baebl)

Cited by 153 publications

References 26 publications

The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL

The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL

Polymorphism in the Plasmodium falciparum erythrocyte-binding ligand JESEBL/EBA-181 alters its receptor specificity

Crystal and Solution Structures of Plasmodium falciparum Erythrocyte-binding Antigen 140 Reveal Determinants of Receptor Specificity during Erythrocyte Invasion

Contact Info

Product

Resources

About