title: Crystal structure of extracellular domain of human lectin-like transcript 1 (LLT1), the ligand for natural killer receptor-P1A.
abstract: Emerging evidence has revealed the pivotal roles of C-type lectin-like receptors (CTLRs) in the regulation of a wide range of immune responses. Human natural killer cell receptor-P1A (NKRP1A) is one of the CTLRs and recognizes another CTLR, lectin-like transcript 1 (LLT1) on target cells to control NK, NKT and Th17 cells. The structural basis for the NKRP1A-LLT1 interaction was limitedly understood. Here, we report the crystal structure of the ectodomain of LLT1. The plausible receptor-binding face of the C-type lectin-like domain is flat, and forms an extended β-sheet. The residues of this face are relatively conserved with another CTLR, keratinocyte-associated C-type lectin, which binds to the CTLR member, NKp65. A LLT1-NKRP1A complex model, prepared using the crystal structures of LLT1 and the keratinocyte-associated C-type lectin-NKp65 complex, reasonably satisfies the charge consistency and the conformational complementarity to explain a previous mutagenesis study. Furthermore, crystal packing and analytical ultracentrifugation revealed dimer formation, which supports a complex model. Our results provide structural insights for understanding the binding modes and signal transduction mechanisms, which are likely to be conserved in the CTLR family, and for further rational drug design towards regulating the LLT1 function.
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kita
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.|Department of Materials Structure Science, Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), The Graduate University for Advanced Studies, Tsukuba, Ibaraki, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Matsubara
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kasai
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Tamaoki
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.|Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okabe
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kamishikiryo
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan.|U-Medico Corporation, Osaka, Japan.
authors.forename: Elena
authors.initials: E
authors.lastname: Krayukhina
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Ose
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C400041:CLEC2D protein, human; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D008024:Ligands; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011956:Receptors, Cell Surface
keywords: C-type lectin-like receptor; Cell surface receptor; Crystal structure; Natural killer cell; Protein-protein interactions