A Novel Mechanism of Carbohydrate Recognition by the C-type Lectins DC-SIGN and DC-SIGNR

DC-SIGN and DC-SIGNR are cell-surface receptors that mediate cell-cell interactions within the immune system by binding to intercellular adhesion molecule-3. The receptor polypeptides share 77% amino acid sequence identity and are type II transmembrane proteins. The extracellular domain of each comprises seven 23-residue tandem repeats and a C-terminal C-type carbohydrate-recognition domain (CRD). Cross-linking, equilibrium ultracentrifugation, and circular dichroism studies of soluble recombinant fragments of DC-SIGN and DC-SIGNR have been used to show that the extracellular domain of each receptor is a tetramer stabilized by an α-helical stalk. Both DC-SIGN and DC-SIGNR bind ligands bearing mannose and related sugars through the CRDs. The CRDs of DC-SIGN and DC-SIGNR bind Man9GlcNAc2 oligosaccharide 130- and 17-fold more tightly than and a bearing is by a of to that the CRDs oligosaccharide binding that the CRDs are the extracellular a of by DC-SIGN and to the of receptors the of to DC-SIGN and DC-SIGNR are cell-surface receptors that mediate cell-cell interactions within the immune system by binding to intercellular adhesion molecule-3. The receptor polypeptides share 77% amino acid sequence identity and are type II transmembrane proteins. The extracellular domain of each comprises seven 23-residue tandem repeats and a C-terminal C-type carbohydrate-recognition domain (CRD). Cross-linking, equilibrium ultracentrifugation, and circular dichroism studies of soluble recombinant fragments of DC-SIGN and DC-SIGNR have been used to show that the extracellular domain of each receptor is a tetramer stabilized by an α-helical stalk. Both DC-SIGN and DC-SIGNR bind ligands bearing mannose and related sugars through the CRDs. The CRDs of DC-SIGN and DC-SIGNR bind Man9GlcNAc2 oligosaccharide 130- and 17-fold more tightly than and a bearing is by a of to that the CRDs oligosaccharide binding that the CRDs are the extracellular a of by DC-SIGN and to the of receptors the of to intercellular adhesion domain a cell-surface C-type been to mediate interactions and by binding interactions are of is the DC-SIGN the of and of The DC-SIGN is to a a related DC-SIGNR of DC-SIGNR have to bind and to is the of and than of DC-SIGN are DC-SIGNR and DC-SIGNR are type II transmembrane that share 77% amino acid sequence identity The extracellular domain of each of a of seven and a tandem repeats of a sequence of amino by a C-terminal C-type domain (CRD). 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DC-SIGNR are the of each amino acid a of that is each a the circular dichroism that the repeats an α-helical a of the extracellular domain fragments of DC-SIGN and the receptors are and of of to the sequence DC-SIGN and DC-SIGNR and the studies that are show binding the ligands binding are the and the that the CRDs and is that of DC-SIGNR than the and are to DC-SIGN and the receptors to by a cell-surface C-type been to mediate interactions and by binding interactions are of is the DC-SIGN the of and of The DC-SIGN is to a a related DC-SIGNR of DC-SIGNR have to bind and to is the of and than of DC-SIGN are DC-SIGNR DC-SIGN and DC-SIGNR are type II transmembrane that share 77% amino acid sequence identity The extracellular domain of each of a of seven and a tandem repeats of a sequence of amino by a C-terminal C-type domain (CRD). 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polypeptides a fragments of DC-SIGN and DC-SIGNR are to of the the an that are by to the that are than of the extracellular of DC-SIGN and DC-SIGNR binding to the Both DC-SIGN and DC-SIGNR bind mannose than bind of the the of is than C-type of to C-type CRDs through interactions the and of the by is to than by a that DC-SIGN and C-type through of the and and the ligands have an binding to the extracellular domain fragments of DC-SIGN and each by are each are a Both DC-SIGN and DC-SIGNR show and more than is by of the of mannose the binding of to DC-SIGNR is than binding to DC-SIGN than mannose DC-SIGNR mannose than The of the extracellular of DC-SIGN and DC-SIGNR binding to the Both DC-SIGN and DC-SIGNR bind mannose than bind of the the of is than C-type of to C-type CRDs through interactions the and of the by is to than by a that DC-SIGN and C-type through of the and and the ligands have an each by are each are Both DC-SIGN and DC-SIGNR show and more than is by of the of mannose the 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