GLYCAN INTERACTIONS WITH THE MAMMALIAN LECTIN, DC-SIGN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. DC-SIGN (dendridic cell specific intercellular adhesion molecule grabbing non-integrin) is a type II membrane protein with a 162 residue C-type lectin extracellular domain. DC-SIGN is primarily expressed in dendridic cells where its main function is binding to mannose and fucose containing ligands (include Lewis-x structures) on pathogens. Binding to pathogens results in internalization and targeting to lysosomal compartments for loading of antigen onto MHC class II molecules, as well as the production of additional immune response signals. DC-SIGN, however, also binds to native glycans requiring a careful balance of immune response signals. Imbalance has important consequences for auto-immune disease and downstream consequences for other diseases, including diabetes. Structures for DC-SIGn in complex with some ligands have been determined by X-ray crystallography, but structural investigations spanning the full variety of glycans of interest, including glycosylated peptides and proteins is absent. The object of this collaboration is to allow the Resource to provide some of its sparse labeling NMR technology and some of its glycan production technology to a structure determination project run jointly by Professors Dan Mitchell and Ann Dixon of the University of Warwick.