title: Structural Basis Underlying the Binding Preference of Human Galectins-1, -3 and -7 for Galβ1-3/4GlcNAc.
abstract: Galectins represent β-galactoside-binding proteins and are known to bind Galβ1-3/4GlcNAc disaccharides (abbreviated as LN1 and LN2, respectively). Despite high sequence and structural homology shared by the carbohydrate recognition domain (CRD) of all galectin members, how each galectin displays different sugar-binding specificity still remains ambiguous. Herein we provided the first structural evidence of human galectins-1, 3-CRD and 7 in complex with LN1. Galectins-1 and 3 were shown to have higher affinity for LN2 than for LN1, while galectin-7 displayed the reversed specificity. In comparison with the previous LN2-complexed structures, the results indicated that the average glycosidic torsion angle of galectin-bound LN1 (ψ(LN1) ≈ 135°) was significantly differed from that of galectin-bound LN2 (ψ(LN2 )≈ -108°), i.e. the GlcNAc moiety adopted a different orientation to maintain essential interactions. Furthermore, we also identified an Arg-Asp/Glu-Glu-Arg salt-bridge network and the corresponding loop (to position the second Asp/Glu residue) critical for the LN1/2-binding preference.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Tung-Ju
authors.initials: TJ
authors.lastname: Hsieh
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; Department of Chemistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsien-Ya
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Zhijay
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; Department of Chemistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Bo-Shun
authors.initials: BS
authors.lastname: Huang
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Shang-Chuen
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; The Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Chemistry, National Taiwan University, Taipei, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D001798:Blood Proteins; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism*; D005697:Galactosides / Q000737:chemistry / Q000378:metabolism*; D037483:Galectin 1 / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; D004187:Disaccharides; D005697:Galactosides; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C445499:LGALS1 protein, human; C428445:LGALS3 protein, human; C092525:LGALS7 protein, human; C007816:beta-galactoside