2024-03-29T06:31:39Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1678322020-12-09T17:45:41Zcom_10261_34com_10261_5col_10261_287
00925njm 22002777a 4500
dc
Silva-Martín, Noella
author
Bartual, Sergio G.
author
Ramírez-Aportela, Erney
author
Chacón, Pablo
author
Park, C.G.
author
Hermoso, Juan A.
author
2014
© 2014 Elsevier Ltd. 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 α-2,6-sialylated glycoproteins. Unexpectedly, an additional binding site has been found in the SIGN-R1 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 SIGN-R1 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.
Structure 22: 1595- 1606 (2014)
http://hdl.handle.net/10261/167832
10.1016/j.str.2014.09.001
Structural basis for selective recognition of endogenous and microbial polysaccharides by macrophage receptor SIGN-R1