title: A platform of C-type lectin-like receptor CLEC-2 for binding O-glycosylated podoplanin and nonglycosylated rhodocytin.
abstract: Podoplanin is a transmembrane O-glycoprotein that binds to C-type lectin-like receptor 2 (CLEC-2). The O-glycan-dependent interaction seems to play crucial roles in various biological processes, such as platelet aggregation. Rhodocytin, a snake venom, also binds to CLEC-2 and aggregates platelets in a glycan-independent manner. To elucidate the structural basis of the glycan-dependent and independent interactions, we performed comparative crystallographic studies of podoplanin and rhodocytin in complex with CLEC-2. Both podoplanin and rhodocytin bind to the noncanonical "side" face of CLEC-2. There is a common interaction mode between consecutive acidic residues on the ligands and the same arginine residues on CLEC-2. Other interactions are ligand-specific. Carboxyl groups from the sialic acid residue on podoplanin and from the C terminus of the rhodocytin α subunit interact differently at this "second" binding site on CLEC-2. The unique and versatile binding modes open a way to understand the functional consequences of CLEC-2-ligand interactions.
authors.affiliation: Structural Glycobiology 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: Masamichi
authors.initials: M
authors.lastname: Nagae
authors.affiliation: Structural Glycobiology 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: Kana
authors.initials: K
authors.lastname: Morita-Matsumoto
authors.affiliation: Structural Glycobiology 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: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Mika Kato
authors.initials: MK
authors.lastname: Kaneko
authors.affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Structural Glycobiology Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: yyoshiki@riken.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006031:Glycosylation; D037181:Lectins, C-Type / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D010974:Platelet Aggregation; D011485:Protein Binding; D014757:Viper Venoms / Q000378:metabolism*
chemical_list: D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D014757:Viper Venoms; C112292:rhodocytin protein, Calloselasma rhodostoma