title: The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer.
abstract: The dendritic cell-specific ICAM-3 non-integrin (DC-SIGN) and its close relative DC-SIGNR recognize various glycoproteins, both pathogenic and cellular, through the receptor lectin domain-mediated carbohydrate recognition. While the carbohydrate-recognition domains (CRD) exist as monomers and bind individual carbohydrates with low affinity and are permissive in nature, the full-length receptors form tetramers through their repeat domain and recognize specific ligands with high affinity. To understand the tetramer-based ligand binding avidity, we determined the crystal structure of DC-SIGNR with its last repeat region. Compared to the carbohydrate-bound CRD structure, the structure revealed conformational changes in the calcium and carbohydrate coordination loops of CRD, an additional disulfide bond between the N and the C termini of the CRD, and a helical conformation for the last repeat. On the basis of the current crystal structure and other published structures with sequence homology to the repeat domain, we generated a tetramer model for DC-SIGN/R using homology modeling and propose a ligand-recognition index to identify potential receptor ligands.
authors.affiliation: Laboratory of Immunogenetics, Structural Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Snyder
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D050260:Carbohydrate Metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D011956:Receptors, Cell Surface; D002118:Calcium