title: The structures of glycophorin C N-glycans, a putative component of the GPC receptor site for Plasmodium falciparum EBA-140 ligand.
abstract: Glycophorins C and D are highly glycosylated integral sialoglycoproteins of human red blood cell membranes carrying the Gerbich blood group antigens. The O- and N-glycosidic chains of the major erythrocyte glycoprotein (Lisowska E. 2001, Antigenic properties of human glycophorins - an update. Adv Exp Med Biol, 491:155-169; Tomita M and Marchesi VT. 1975, Amino-acid sequence and oligosaccharide attachment sites of human erythrocyte glycophorin. Proc Natl Acad Sci USA, 72:2964-2968.) are well characterized but the structure of GPC N-glycans has remained unknown. This problem became important since it was reported that GPC N-glycans play an essential role in the interaction with Plasmodium falciparum EBA-140 merozoite ligand. The elucidation of these structures seems essential for full characterization of the GPC binding site for the EBA-140 ligand. We have employed detailed structural analysis using sequential mass spectrometry to show that many GPC N-glycans contain H2 antigen structures and several contain polylactosamine structures capped with fucose. The results obtained indicate structural heterogeneity of the GPC N-glycans and show the existence of structural elements not found in glycophorin A N-glycans. Our results also open a possibility of new interpretation of the data concerning the binding of P. falciparum EBA-140 ligand to GPC. We hypothesize that preferable terminal fucosylation of N-glycosidic chains containing repeating lactosamine units of the GPC Gerbich variant could be an explanation for why the EBA-140 ligand does not react with GPC Gerbich and an indication that the EBA-140 interaction with GPC is distinctly dependent on the GPC N-glycan structure.
authors.affiliation: The Glycomics Center, University of New Hampshire, Durham, NH 03824, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Ashline
authors.affiliation: Polish Academy of Sciences, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Duk
authors.affiliation: Polish Academy of Sciences, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lukasiewicz
authors.affiliation: The Glycomics Center, University of New Hampshire, Durham, NH 03824, USA.
authors.forename: Vernon N
authors.initials: VN
authors.lastname: Reinhold
authors.affiliation: Polish Academy of Sciences, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Elwira
authors.initials: E
authors.lastname: Lisowska
authors.affiliation: Polish Academy of Sciences, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland jaskiew@iitd.pan.wroc.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jaskiewicz
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D006021:Glycophorins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C438380:EBA140 protein, Plasmodium falciparum; D006021:Glycophorins; D008565:Membrane Proteins; D011134:Polysaccharides; D015800:Protozoan Proteins
keywords: EBA-140 ligand; Plasmodium; glycan; glycophorin; mass spectrometry