title: Structural basis for simultaneous recognition of an O-glycan and its attached peptide of mucin family by immune receptor PILRα.
abstract: Paired Ig-like type 2 receptor α (PILRα) recognizes a wide range of O-glycosylated mucin and related proteins to regulate broad immune responses. However, the molecular characteristics of these recognitions are largely unknown. Here we show that sialylated O-linked sugar T antigen (sTn) and its attached peptide region are both required for ligand recognition by PILRα. Furthermore, we determined the crystal structures of PILRα and its complex with an sTn and its attached peptide region. The structures show that PILRα exhibits large conformational change to recognize simultaneously both the sTn O-glycan and the compact peptide structure constrained by proline residues. Binding and functional assays support this binding mode. These findings provide significant insight into the binding motif and molecular mechanism (which is distinct from sugar-recognition receptors) by which O-glycosylated mucin proteins with sTn modifications are recognized in the immune system as well as during viral entry.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan;
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan;
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan;
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Ose
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Munechika
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Tabata
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Nobuo
authors.initials: N
authors.lastname: Maita
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Seiko
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kajikawa
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan;
authors.forename: Amane
authors.initials: A
authors.lastname: Kogure
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan;
authors.forename: Takeshi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan;Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; andCore Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan arase@biken.osaka-u.ac.jp maenaka@pharm.hokudai.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan;Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan arase@biken.osaka-u.ac.jp maenaka@pharm.hokudai.ac.jp.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D007107:Immune System; D008562:Membrane Glycoproteins / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D016296:Mutagenesis; D010455:Peptides / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D008562:Membrane Glycoproteins; D009077:Mucins; C412263:PILRA protein, human; D010455:Peptides; D011134:Polysaccharides; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins
keywords: O-glycosylated protein; X-ray crystallography; immune regulation; paired receptor