Carbohydrate recognition properties of human ficolins: glycan array screening reveals the sialic acid binding specificity of M-ficolin
| Autor: | Gout, Evelyne, Garlatti, Virginie, Smith, David F, Lacroix, Monique, Dumestre-Pérard, Chantal, Lunardi, Thomas, Martin, Lydie, Cesbron, Jean-Yves, Arlaud, Gérard J, Gaboriaud, Christine, Thielens, Nicole |
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| Přispěvatelé: | Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry, Emory University [Atlanta, GA], Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
Carbohydrates
Mutation Missense Protein Array Analysis Glycobiology and Extracellular Matrices Crystallography X-Ray MESH: Tyrosine MESH: Lectins Polysaccharides Lectins MESH: Protein Binding Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mutation Missense MESH: Humans MESH: Protein Array Analysis Fibrinogen MESH: Crystallography X-Ray N-Acetylneuraminic Acid MESH: Mutagenesis Site-Directed MESH: Polysaccharides MESH: Fibrinogen Mutagenesis Site-Directed Tyrosine MESH: N-Acetylneuraminic Acid MESH: Carbohydrates Protein Binding |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (9), pp.6612-22. ⟨10.1074/jbc.M109.065854⟩ Journal of Biological Chemistry, 2010, 285 (9), pp.6612-22. ⟨10.1074/jbc.M109.065854⟩ |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | International audience; Ficolins are oligomeric innate immune recognition proteins consisting of a collagen-like region and a fibrinogen-like recognition domain that bind to pathogen- and apoptotic cell-associated molecular patterns. To investigate their carbohydrate binding specificities, serum-derived L-ficolin and recombinant H- and M-ficolins were fluorescently labeled, and their carbohydrate binding ability was analyzed by glycan array screening. L-ficolin preferentially recognized disulfated N-acetyllactosamine and tri- and tetrasaccharides containing terminal galactose or N-acetylglucosamine. Binding was sensitive to the position and orientation of the bond between N-acetyllactosamine and the adjacent carbohydrate. No significant binding of H-ficolin to any of the 377 glycans probed could be detected, providing further evidence for its poor lectin activity. M-ficolin bound preferentially to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage. To further investigate the structural basis of sialic acid recognition by M-ficolin, point mutants were produced in which three residues of the fibrinogen domain were replaced by their counterparts in L-ficolin. Mutations G221F and A256V inhibited binding to the 9-O-acetylated sialic acid derivatives, whereas Y271F abolished interaction with all sialic acid-containing glycans. The crystal structure of the Y271F mutant fibrinogen domain was solved, showing that the mutation does not alter the structure of the ligand binding pocket. These analyses reveal novel ficolin ligands such as sulfated N-acetyllactosamine (L-ficolin) and gangliosides (M-ficolin) and provide precise insights into the sialic acid binding specificity of M-ficolin, emphasizing the essential role of Tyr(271) in this respect. |
| Databáze: | OpenAIRE |
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