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Caenorhabditis elegans galectins LEC-6 and LEC-1 recognize a chemically synthesized Gal 1-4Fuc disaccharide unit which is present in Protostomia glycoconjugates

2009; Oxford University Press; Volume: 19; Issue: 12 Linguagem: Inglês

10.1093/glycob/cwp125

1460-2423

Tomoharu Takeuchi, K. Nishiyama, Ken-ichi Sugiura, Miki Takahashi, Atsushi Yamada, Susumu Kobayashi, Hideyo Takahashi, Hideaki Natsugari, Ken‐ichi Kasai,

Signaling Pathways in Disease

Galβ1-4GlcNAc is thought to be a common disaccharide unit preferentially recognized by vertebrate galectins. Eight-amino-acid residues conserved in proteins belonging to the galectin family have been suggested to be responsible for recognition. Meanwhile, we isolated and analyzed endogenous N-glycans of Caenorhabditis elegans that were captured by a C. elegans galectin LEC-6 and demonstrated that the unit of recognition for LEC-6 is a Gal-Fuc disaccharide, though the linkage between these residues was not confirmed. In the present study, we chemically synthesized Galβ1-4Fuc and Galβ1-3Fuc labeled with 2-aminopyridine (PA) and demonstrated that LEC-6 interacts with PA-Galβ1-4Fuc more strongly than PA-Galβ1-3Fuc by frontal affinity chromatography (FAC). Galβ1-4Fuc also inhibited hemagglutination caused by LEC-6 more strongly than Galβ1-3Fuc. FAC analysis using LEC-6 point mutants revealed that some of the conserved amino acid residues which have proven to be important for the recognition of Galβ1-4GlcNAc are not necessary for the binding to Galβ1-4Fuc. Another major C. elegans galectin, LEC-1, also showed preferential binding to Galβ1-4Fuc. These results suggest that Galβ1-4Fuc is the endogenous unit structure recognized by C. elegans galectins, which implies that C. elegans glycans and galectins may have co-evolved through an alteration in the structures of C. elegans glycans and a subsequent conversion in the sugar-binding mechanism of galectins. Furthermore, since glycans containing the Galβ1-4Fuc disaccharide unit have been found in organisms belonging to Protostomia, this unit might be a common glyco-epitope recognized by galectins in these organisms.