title: Atomic visualization of a flipped-back conformation of bisected glycans bound to specific lectins.
abstract: Glycans normally exist as a dynamic equilibrium of several conformations. A fundamental question concerns how such molecules bind lectins despite disadvantageous entropic loss upon binding. Bisected glycan, a glycan possessing bisecting N-acetylglucosamine (GlcNAc), is potentially a good model for investigating conformational dynamics and glycan-lectin interactions, owing to the unique ability of this sugar residue to alter conformer populations and thus modulate the biological activities. Here we analyzed bisected glycan in complex with two unrelated lectins, Calsepa and PHA-E. The crystal structures of the two complexes show a conspicuous flipped back glycan structure (designated 'back-fold' conformation), and solution NMR analysis also provides evidence of 'back-fold' glycan structure. Indeed, statistical conformational analysis of available bisected and non-bisected glycan structures suggests that bisecting GlcNAc restricts the conformations of branched structures. Restriction of glycan flexibility by certain sugar residues may be more common than previously thought and impinges on the mechanism of glycoform-dependent biological functions.
authors.affiliation: Structural Glycobiology Team, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nagae
authors.affiliation: Structural Glycobiology Team, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kanagawa
authors.affiliation: Structural Glycobiology Team, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Morita-Matsumoto
authors.affiliation: Department of Chemistry, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hanashima
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kizuka
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.affiliation: Structural Glycobiology Team, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018345:Mice, Knockout; D008958:Models, Molecular; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics; D010835:Phytohemagglutinins / Q000737:chemistry / Q000378:metabolism; D037121:Plant Lectins / Q000737:chemistry* / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: D010835:Phytohemagglutinins; D037121:Plant Lectins; D011134:Polysaccharides; C067494:erythroagglutinating phytohemagglutinin; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine