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Bikunin proteins and tumor necrosis factor stimulated gene-6 protein (TSG-6)

Tania Aaquist Nielsen, Ida B. Thøgersen, Camilla Lund Nikolajsen, Lone Hansen, Carsten S. Sonne-Schmidt, Kristian Sanggaard

The bikunin proteins comprise a family of multi-chain serine protease inhibitors composed of the proteoglycan bikunin alone or in complex with one or two homologous heavy chains. The proteins are present in plasma in relatively high concentrations, although their function here remains unclear. The bikunin family is characterized by a unique covalent linkage between the C-terminal of the heavy chains and a chondroitin sulfate chain (a glycosaminoglycan) originating from Ser-10 of bikunin. We have previously determined the structure of this linkage, designated a protein-glycosaminoglycan-protein (PGP) cross-link.

IalphaI crosslink


The bikunin proteins interact with tumor necrosis factor stimulated gene-6 protein (TSG-6) and in concert these proteins play a role at different physiological conditions, including infertility (mice studies) and inflammatory diseases (e.g. arthritis). In the presence of hyaluronan (a glycosaminoglycan) the interaction of bikunin proteins and TSG-6 results in a transfer of heavy chains from bikunin proteins to hyaluronan. The generation of heavy chain•hyaluronan complexes is thought to stabilize the extracellular matrix.

Research is carried out to further understand the structure and biology of these unique proteins, and to elucidate the mechanism of interaction between bikunin proteins, TSG-6, and glycosaminoglycans.