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Tomomitsu Hatakeyama - One of the best experts on this subject based on the ideXlab platform.
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novel carbohydrate recognition mode of the invertebrate c type lectin spl 1 from saxidomus purpuratus revealed by the glcnac complex crystal in the presence of ca2
Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2020Co-Authors: Hideaki Unno, Shuhei Higuchi, Shuichiro Goda, Tomomitsu HatakeyamaAbstract:The C-Type Lectins SPL-1 and SPL-2 from the bivalve Saxidomus purpuratus are composed of A and B chains and of two B chains, respectively. They bind specific carbohydrates containing acetamido groups, such as N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc), in a Ca2+-independent manner. Unlike ordinary C-Type Lectins, which require Ca2+ ions for carbohydrate recognition, these Lectins recognize specific carbohydrates mainly through interactions with the acetamido group without Ca2+ ions, even though Ca2+ enhances the binding affinity of these Lectins, especially SPL-1. In the present study, the crystal structure of the SPL-1-GlcNAc complex in the presence of Ca2+ revealed that the binding of SPL-1 to GlcNAc is stabilized by hydrogen bonds to the water molecule(s) coordinating Ca2+, whereas in ordinary C-Type Lectins Ca2+ directly forms coordinate bonds to the hydroxy groups of carbohydrates. These differences may also allow SPL-1 and SPL-2 to recognize both GlcNAc and GalNAc, which have different orientations of the 4-hydroxy group.
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novel ca2 independent carbohydrate recognition of the c type Lectins spl 1 and spl 2 from the bivalve saxidomus purpuratus
Protein Science, 2019Co-Authors: Hideaki Unno, Shuhei Higuchi, Shuichiro Goda, Shuhei Itakura, Kenichi Yamaguchi, Tomomitsu HatakeyamaAbstract:: Novel Ca2+ -independent C-Type Lectins, SPL-1 and SPL-2, were purified from the bivalve Saxidomus purpuratus. They are composed of dimers with either identical (SPL-2 composed of two B-chains) or distinct (SPL-1 composed of A- and B-chains) polypeptide chains, and show affinity for N-acetylglucosamine (GlcNAc)- and N-acetylgalactosamine (GalNAc)-containing carbohydrates, but not for glucose or galactose. A database search for sequence similarity suggested that they belong to the C-Type lectin family. X-ray crystallographic analysis revealed definite structural similarities between their subunits and the carbohydrate-recognition domain (CRD) of the C-Type lectin family. Nevertheless, these Lectins (especially SPL-2) showed Ca2+ -independent binding affinity for GlcNAc and GalNAc. The crystal structure of SPL-2/GalNAc complex revealed that bound GalNAc was mainly recognized via its acetamido group through stacking interactions with Tyr and His residues and hydrogen bonds with Asp and Asn residues, while widely known carbohydrate-recognition motifs among the C-Type CRD (the QPD [Gln-Pro-Asp] and EPN [Glu-Pro-Asn] sequences) are not involved in the binding of the carbohydrate. Carbohydrate-binding specificities of individual A- and B-chains were examined by glycan array analysis using recombinant Lectins produced from Escherichia coli cells, where both subunits preferably bound oligosaccharides having terminal GlcNAc or GalNAc with α-glycosidic linkages with slightly different specificities.
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Novel Ca2+‐independent carbohydrate recognition of the C‐type Lectins, SPL‐1 and SPL‐2, from the bivalve Saxidomus purpuratus
Protein Science, 2019Co-Authors: Hideaki Unno, Shuhei Higuchi, Shuichiro Goda, Shuhei Itakura, Kenichi Yamaguchi, Tomomitsu HatakeyamaAbstract:: Novel Ca2+ -independent C-Type Lectins, SPL-1 and SPL-2, were purified from the bivalve Saxidomus purpuratus. They are composed of dimers with either identical (SPL-2 composed of two B-chains) or distinct (SPL-1 composed of A- and B-chains) polypeptide chains, and show affinity for N-acetylglucosamine (GlcNAc)- and N-acetylgalactosamine (GalNAc)-containing carbohydrates, but not for glucose or galactose. A database search for sequence similarity suggested that they belong to the C-Type lectin family. X-ray crystallographic analysis revealed definite structural similarities between their subunits and the carbohydrate-recognition domain (CRD) of the C-Type lectin family. Nevertheless, these Lectins (especially SPL-2) showed Ca2+ -independent binding affinity for GlcNAc and GalNAc. The crystal structure of SPL-2/GalNAc complex revealed that bound GalNAc was mainly recognized via its acetamido group through stacking interactions with Tyr and His residues and hydrogen bonds with Asp and Asn residues, while widely known carbohydrate-recognition motifs among the C-Type CRD (the QPD [Gln-Pro-Asp] and EPN [Glu-Pro-Asn] sequences) are not involved in the binding of the carbohydrate. Carbohydrate-binding specificities of individual A- and B-chains were examined by glycan array analysis using recombinant Lectins produced from Escherichia coli cells, where both subunits preferably bound oligosaccharides having terminal GlcNAc or GalNAc with α-glycosidic linkages with slightly different specificities.
Gordon D. Brown - One of the best experts on this subject based on the ideXlab platform.
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C-Type Lectins in immunity and homeostasis
Nature Reviews Immunology, 2018Co-Authors: Gordon D. Brown, Janet A. Willment, Lauren WhiteheadAbstract:The C-Type Lectins are a superfamily of proteins that recognize a broad repertoire of ligands and that regulate a diverse range of physiological functions. Most research attention has focused on the ability of C-Type Lectins to function in innate and adaptive antimicrobial immune responses, but these proteins are increasingly being recognized to have a major role in autoimmune diseases and to contribute to many other aspects of multicellular existence. Defects in these molecules lead to developmental and physiological abnormalities, as well as altered susceptibility to infectious and non-infectious diseases. In this Review, we present an overview of the roles of C-Type Lectins in immunity and homeostasis, with an emphasis on the most exciting recent discoveries. Recently discovered roles for C-Type Lectins in development, homeostasis, cell death, cancer and autoimmune and inflammatory diseases extend the functions of this superfamily beyond their well-recognized involvement in antimicrobial responses.
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C-Type Lectins in immunity and homeostasis.
Nature Reviews Immunology, 2018Co-Authors: Gordon D. Brown, Janet A. Willment, Lauren WhiteheadAbstract:The C-Type Lectins are a superfamily of proteins that recognize a broad repertoire of ligands and that regulate a diverse range of physiological functions. Most research attention has focused on the ability of C-Type Lectins to function in innate and adaptive antimicrobial immune responses, but these proteins are increasingly being recognized to have a major role in autoimmune diseases and to contribute to many other aspects of multicellular existence. Defects in these molecules lead to developmental and physiological abnormalities, as well as altered susceptibility to infectious and non-infectious diseases. In this Review, we present an overview of the roles of C-Type Lectins in immunity and homeostasis, with an emphasis on the most exciting recent discoveries.
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c type Lectins in immunity recent developments
Current Opinion in Immunology, 2015Co-Authors: Ivy M Dambuza, Gordon D. BrownAbstract:C-Type lectin receptors (CLRs) comprise a large superfamily of proteins, which recognise a diverse range of ligands, and are defined by the presence of at least one C-Type lectin-like domain (CTLD). Of particular interest are the single extracellular CTLD-containing receptors of the ‘Dectin-1’ and ‘Dectin-2’ clusters, which associate with signalling adaptors or possess integral intracellular signalling domains. These CLRs have traditionally been associated with the recognition of fungi, but recent discoveries have revealed diverse and unexpected functions. In this review, we describe their newly identified roles in anti-microbial host defence, homeostasis, autoimmunity, allergy and their functions in the recognition and response to dead and cancerous cells.
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Signalling C-Type Lectins in Antimicrobial Immunity
PLoS pathogens, 2013Co-Authors: Rebecca A. Drummond, Gordon D. BrownAbstract:Since it was first proposed that the innate immune system could recognise conserved microbial-associated molecular patterns (or PAMPs) through inherited receptors expressed by the host (termed pattern recognition receptors, or PRRs), several families of PRRs have been discovered and characterised. The most famous of these are the Toll-like receptors (TLRs), but there is growing appreciation that another large family of PRRs, known as the C-Type lectin receptors (CLRs), also play a major role in antimicrobial immunity. CLRs have one or more carbohydrate recognition domains (CRDs) that recognise a wide variety of carbohydrate ligands. Other members of the CLR family, which do not recognise carbohydrate ligands but contain similar protein folds called C-Type lectin-like domains (CTLD), have also been discovered and are included in this large family whose members are divided into 17 groups relating to phylogeny and structure. Upon ligand binding, some CLRs (such as Dectin-1, Dectin-2, and Mincle) undergo intracellular signalling to drive cellular responses. Here, we outline the signalling pathways downstream of these receptors and discuss how they, and some other CLRs (including the Mannose Receptor, CLEC5A, CLEC9A, and DC-SIGN), contribute to immunity against fungi, bacteria, viruses, and parasites.
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C-Type lectin receptors and cytokines in fungal immunity
Cytokine, 2011Co-Authors: Simon Vautier, Donna M. Maccallum, Gordon D. BrownAbstract:Fungi are the cause of opportunistic infections, predominantly in immunocompromised individuals although, primary fungal infections can occur in apparently healthy individuals. Successful host defence requires an effective innate and adaptive immune response. Central to host immune responses are the induction of cytokines; the signals which help to activate the innate immune system and which play a central role in directing the development of pathogen-specific immunity. C-Type Lectins play a central role in the recognition and shaping of immune responses to fungal pathogens, in part, through the induction and modulation of cytokine responses. Understanding which cytokines induce protective responses to these pathogens and how C-Type Lectins and other receptors direct cytokine production may allow development of novel antifungal therapies. Here we review the C-Type Lectins, their influence on cytokine production and subsequent immune responses in antifungal immunity.
Kayo Inaba - One of the best experts on this subject based on the ideXlab platform.
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functional comparison of the mouse dc sign signr1 signr3 and langerin c type Lectins
International Immunology, 2004Co-Authors: Kazuhiko Takahara, Yusuke Yashima, Yoshiki Omatsu, Hideo Yoshida, Yukino Kimura, Young Sun Kang, Ralph M Steinman, Chae Gyu Park, Kayo InabaAbstract:The mouse (m) DC-SIGN family consists of several homologous type II transmembrane proteins located in close proximity on chromosome 8 and having a single carboxyl terminal carbohydrate recognition domain. We first used transfected non-macrophage cell lines to compare the polysaccharide and microbial uptake capacities of three of these Lectins--DC-SIGN, SIGNR1 and SIGNR3--to another homologue mLangerin. Each molecule shares a potential mannose-recognition EPN-motif in its carbohydrate recognition domain. Using an anti-Tag antibody to follow Tag-labeled transfectants, we found that each molecule could be internalized, although the rates differed. However, mDC-SIGN was unable to take up FITC-dextran, FITC-ovalbumin, zymosan or heat-killed Candida albicans. The other three Lectins showed distinct carbohydrate recognition properties, assessed by blocking FITC-dextran uptake at 37 degrees C and by mannan binding activity at 4 degrees C. Furthermore, only SIGNR1 was efficient in mediating the capture by transfected cells of Gram-negative bacteria, such as Escherichia coli and Salmonella typhimurium, while none of the Lectins tested were competent to capture Gram-positive bacteria, Staphylococcus aureus. Interestingly, transfectants with SIGNR1 lacking the cytoplasmic domain were capable of binding FITC-zymosan in a manner that was abolished by EDTA or mannan, but not laminarin. In addition, resident peritoneal CD11b+ cells expressing SIGNR1 bound zymosan at 4 degrees C in concert with a laminarin-sensitive receptor. Therefore these homologous C-Type Lectins have distinct recognition patters for microbes despite similarities in the carbohydrate recognition domains.
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functional comparison of the mouse dc sign signr1 signr3 and langerin c type Lectins
International Immunology, 2004Co-Authors: Kazuhiko Takahara, Yusuke Yashima, Yoshiki Omatsu, Hideo Yoshida, Yukino Kimura, Young Sun Kang, Ralph M Steinman, Chae Gyu Park, Kayo InabaAbstract:The mouse (m) DC-SIGN family consists of several homologous type II transmembrane proteins located in close proximity on chromosome 8 and having a single carboxyl terminal carbohydrate recognition domain. We first used transfected non-macrophage cell lines to compare the polysaccharide and microbial uptake capacities of three of these Lectins—DC-SIGN, SIGNR1 and SIGNR3—to another homologue mLangerin. Each molecule shares a potential mannose-recognition EPN-motif in its carbohydrate recognition domain. Using an anti-Tag antibody to follow Tag-labeled transfectants, we found that each molecule could be internalized, although the rates differed. However, mDC-SIGN was unable to take up FITC‐dextran, FITC‐ovalbumin, zymosan or heat-killed Candida albicans. The other three Lectins showed distinct carbohydrate recognition properties, assessed by blocking FITC‐dextran uptake at 37∞C and by mannan binding activity at 4∞C. Furthermore, only SIGNR1 was efficient in mediating the capture by transfected cells of Gramnegative bacteria, such as Escherichia coli and Salmonella typhimurium, while none of the Lectins tested were competent to capture Gram-positive bacteria, Staphylococcus aureus. Interestingly, transfectants with SIGNR1 lacking the cytoplasmic domain were capable of binding FITC‐zymosan in a manner that was abolished by EDTA or mannan, but not laminarin. In addition, resident peritoneal CD11b + cells expressing SIGNR1 bound zymosan at 4∞C in concert with a laminarinsensitive receptor. Therefore these homologous C-Type Lectins have distinct recognition patters for microbes despite similarities in the carbohydrate recognition domains.
Hideaki Unno - One of the best experts on this subject based on the ideXlab platform.
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novel carbohydrate recognition mode of the invertebrate c type lectin spl 1 from saxidomus purpuratus revealed by the glcnac complex crystal in the presence of ca2
Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2020Co-Authors: Hideaki Unno, Shuhei Higuchi, Shuichiro Goda, Tomomitsu HatakeyamaAbstract:The C-Type Lectins SPL-1 and SPL-2 from the bivalve Saxidomus purpuratus are composed of A and B chains and of two B chains, respectively. They bind specific carbohydrates containing acetamido groups, such as N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc), in a Ca2+-independent manner. Unlike ordinary C-Type Lectins, which require Ca2+ ions for carbohydrate recognition, these Lectins recognize specific carbohydrates mainly through interactions with the acetamido group without Ca2+ ions, even though Ca2+ enhances the binding affinity of these Lectins, especially SPL-1. In the present study, the crystal structure of the SPL-1-GlcNAc complex in the presence of Ca2+ revealed that the binding of SPL-1 to GlcNAc is stabilized by hydrogen bonds to the water molecule(s) coordinating Ca2+, whereas in ordinary C-Type Lectins Ca2+ directly forms coordinate bonds to the hydroxy groups of carbohydrates. These differences may also allow SPL-1 and SPL-2 to recognize both GlcNAc and GalNAc, which have different orientations of the 4-hydroxy group.
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novel ca2 independent carbohydrate recognition of the c type Lectins spl 1 and spl 2 from the bivalve saxidomus purpuratus
Protein Science, 2019Co-Authors: Hideaki Unno, Shuhei Higuchi, Shuichiro Goda, Shuhei Itakura, Kenichi Yamaguchi, Tomomitsu HatakeyamaAbstract:: Novel Ca2+ -independent C-Type Lectins, SPL-1 and SPL-2, were purified from the bivalve Saxidomus purpuratus. They are composed of dimers with either identical (SPL-2 composed of two B-chains) or distinct (SPL-1 composed of A- and B-chains) polypeptide chains, and show affinity for N-acetylglucosamine (GlcNAc)- and N-acetylgalactosamine (GalNAc)-containing carbohydrates, but not for glucose or galactose. A database search for sequence similarity suggested that they belong to the C-Type lectin family. X-ray crystallographic analysis revealed definite structural similarities between their subunits and the carbohydrate-recognition domain (CRD) of the C-Type lectin family. Nevertheless, these Lectins (especially SPL-2) showed Ca2+ -independent binding affinity for GlcNAc and GalNAc. The crystal structure of SPL-2/GalNAc complex revealed that bound GalNAc was mainly recognized via its acetamido group through stacking interactions with Tyr and His residues and hydrogen bonds with Asp and Asn residues, while widely known carbohydrate-recognition motifs among the C-Type CRD (the QPD [Gln-Pro-Asp] and EPN [Glu-Pro-Asn] sequences) are not involved in the binding of the carbohydrate. Carbohydrate-binding specificities of individual A- and B-chains were examined by glycan array analysis using recombinant Lectins produced from Escherichia coli cells, where both subunits preferably bound oligosaccharides having terminal GlcNAc or GalNAc with α-glycosidic linkages with slightly different specificities.
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Novel Ca2+‐independent carbohydrate recognition of the C‐type Lectins, SPL‐1 and SPL‐2, from the bivalve Saxidomus purpuratus
Protein Science, 2019Co-Authors: Hideaki Unno, Shuhei Higuchi, Shuichiro Goda, Shuhei Itakura, Kenichi Yamaguchi, Tomomitsu HatakeyamaAbstract:: Novel Ca2+ -independent C-Type Lectins, SPL-1 and SPL-2, were purified from the bivalve Saxidomus purpuratus. They are composed of dimers with either identical (SPL-2 composed of two B-chains) or distinct (SPL-1 composed of A- and B-chains) polypeptide chains, and show affinity for N-acetylglucosamine (GlcNAc)- and N-acetylgalactosamine (GalNAc)-containing carbohydrates, but not for glucose or galactose. A database search for sequence similarity suggested that they belong to the C-Type lectin family. X-ray crystallographic analysis revealed definite structural similarities between their subunits and the carbohydrate-recognition domain (CRD) of the C-Type lectin family. Nevertheless, these Lectins (especially SPL-2) showed Ca2+ -independent binding affinity for GlcNAc and GalNAc. The crystal structure of SPL-2/GalNAc complex revealed that bound GalNAc was mainly recognized via its acetamido group through stacking interactions with Tyr and His residues and hydrogen bonds with Asp and Asn residues, while widely known carbohydrate-recognition motifs among the C-Type CRD (the QPD [Gln-Pro-Asp] and EPN [Glu-Pro-Asn] sequences) are not involved in the binding of the carbohydrate. Carbohydrate-binding specificities of individual A- and B-chains were examined by glycan array analysis using recombinant Lectins produced from Escherichia coli cells, where both subunits preferably bound oligosaccharides having terminal GlcNAc or GalNAc with α-glycosidic linkages with slightly different specificities.
Kazuhiko Takahara - One of the best experts on this subject based on the ideXlab platform.
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functional comparison of the mouse dc sign signr1 signr3 and langerin c type Lectins
International Immunology, 2004Co-Authors: Kazuhiko Takahara, Yusuke Yashima, Yoshiki Omatsu, Hideo Yoshida, Yukino Kimura, Young Sun Kang, Ralph M Steinman, Chae Gyu Park, Kayo InabaAbstract:The mouse (m) DC-SIGN family consists of several homologous type II transmembrane proteins located in close proximity on chromosome 8 and having a single carboxyl terminal carbohydrate recognition domain. We first used transfected non-macrophage cell lines to compare the polysaccharide and microbial uptake capacities of three of these Lectins--DC-SIGN, SIGNR1 and SIGNR3--to another homologue mLangerin. Each molecule shares a potential mannose-recognition EPN-motif in its carbohydrate recognition domain. Using an anti-Tag antibody to follow Tag-labeled transfectants, we found that each molecule could be internalized, although the rates differed. However, mDC-SIGN was unable to take up FITC-dextran, FITC-ovalbumin, zymosan or heat-killed Candida albicans. The other three Lectins showed distinct carbohydrate recognition properties, assessed by blocking FITC-dextran uptake at 37 degrees C and by mannan binding activity at 4 degrees C. Furthermore, only SIGNR1 was efficient in mediating the capture by transfected cells of Gram-negative bacteria, such as Escherichia coli and Salmonella typhimurium, while none of the Lectins tested were competent to capture Gram-positive bacteria, Staphylococcus aureus. Interestingly, transfectants with SIGNR1 lacking the cytoplasmic domain were capable of binding FITC-zymosan in a manner that was abolished by EDTA or mannan, but not laminarin. In addition, resident peritoneal CD11b+ cells expressing SIGNR1 bound zymosan at 4 degrees C in concert with a laminarin-sensitive receptor. Therefore these homologous C-Type Lectins have distinct recognition patters for microbes despite similarities in the carbohydrate recognition domains.
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functional comparison of the mouse dc sign signr1 signr3 and langerin c type Lectins
International Immunology, 2004Co-Authors: Kazuhiko Takahara, Yusuke Yashima, Yoshiki Omatsu, Hideo Yoshida, Yukino Kimura, Young Sun Kang, Ralph M Steinman, Chae Gyu Park, Kayo InabaAbstract:The mouse (m) DC-SIGN family consists of several homologous type II transmembrane proteins located in close proximity on chromosome 8 and having a single carboxyl terminal carbohydrate recognition domain. We first used transfected non-macrophage cell lines to compare the polysaccharide and microbial uptake capacities of three of these Lectins—DC-SIGN, SIGNR1 and SIGNR3—to another homologue mLangerin. Each molecule shares a potential mannose-recognition EPN-motif in its carbohydrate recognition domain. Using an anti-Tag antibody to follow Tag-labeled transfectants, we found that each molecule could be internalized, although the rates differed. However, mDC-SIGN was unable to take up FITC‐dextran, FITC‐ovalbumin, zymosan or heat-killed Candida albicans. The other three Lectins showed distinct carbohydrate recognition properties, assessed by blocking FITC‐dextran uptake at 37∞C and by mannan binding activity at 4∞C. Furthermore, only SIGNR1 was efficient in mediating the capture by transfected cells of Gramnegative bacteria, such as Escherichia coli and Salmonella typhimurium, while none of the Lectins tested were competent to capture Gram-positive bacteria, Staphylococcus aureus. Interestingly, transfectants with SIGNR1 lacking the cytoplasmic domain were capable of binding FITC‐zymosan in a manner that was abolished by EDTA or mannan, but not laminarin. In addition, resident peritoneal CD11b + cells expressing SIGNR1 bound zymosan at 4∞C in concert with a laminarinsensitive receptor. Therefore these homologous C-Type Lectins have distinct recognition patters for microbes despite similarities in the carbohydrate recognition domains.
