title: Structural basis for selective recognition of endogenous and microbial polysaccharides by macrophage receptor SIGN-R1.
abstract: SIGN-R1 is a principal receptor for microbial polysaccharides uptake and is responsible for C3 fixation via an unusual complement activation pathway on splenic marginal zone macrophages. In these macrophages, SIGN-R1 is also involved in anti-inflammatory activity of intravenous immunoglobulin by direct interaction with sialylated Fcs. The high-resolution crystal structures of SIGN-R1 carbohydrate recognition domain and its complexes with dextran sulfate or sialic acid, and of the sialylated Fc antibody provide insights into SIGN-R1’s selective recognition of a-2,6-sialylated glycoproteins. Unexpectedly, an additional binding site has been found in the SIGNR1 carbohydrate recognition domain, structurally separate from the calcium-dependent carbohydrate-binding site. This secondary binding site could bind repetitive molecular patterns, as observed in microbial polysaccharides, in a calcium-independent manner. These two binding sites may allow SIGNR1 to simultaneously bind both immune glycoproteins and microbial polysaccharide components, accommodating SIGN-R1’s ability to relate the recognition of microbes to the activation of the classical complement pathway.
authors.forename: Noella
authors.initials: N
authors.lastname: Silva-Martín
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Bartual
authors.forename: Erney
authors.initials: E
authors.lastname: Ramírez-Aportela
authors.forename: Pablo
authors.initials: P
authors.lastname: Chacón
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Juan A
authors.initials: JA
authors.lastname: Hermoso
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D003412:Cricetulus; D018360:Crystallography, X-Ray; D016264:Dextran Sulfate / Q000378:metabolism*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016264:Dextran Sulfate; D007141:Immunoglobulin Fc Fragments; D037181:Lectins, C-Type; D019158:N-Acetylneuraminic Acid; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin