The TSG-6/HC2-mediated Transfer Is a Dynamic Process Shuffling Heavy Chains between Glycosaminoglycans |
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Authors: | Kristian W. Sanggaard Carsten Scavenius Anna Julie Rasmussen Hans-Georg Wisniewski Ida B. Th?gersen Jan J. Enghild |
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Affiliation: | From the ‡Center for Insoluble Protein Structures (inSPIN) and Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology, Aarhus University, 8000 Aarhus C, Denmark and ;the §Department of Microbiology, New York University School of Medicine, New York, New York 10016 |
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Abstract: | The heavy chain (HC) subunits of the bikunin proteins are covalently attached to a single chondroitin sulfate (CS) chain originating from bikunin and can be transferred to different hyaluronan (HA) molecules by TSG-6/HC2. In the present study, we demonstrate that HCs transferred to HA may function as HC donors in subsequent transfer reactions, and we show that the CS of bikunin may serve as an HC acceptor, analogous to HA. Our data suggest that TSG-6/HC2 link HCs randomly on the CS chain of bikunin, in contrast to the ordered attachment observed during the biosynthesis. Moreover, the results show that the transfer activity is indifferent to the new HC position, and the relocated HCs are thus prone to further TSG-6/HC2-induced transfer reactions. The data suggest that HCs may be transferred directly from HA to HA without the involvement of the bikunin CS chain. The results demonstrate reversibility of the interactions between HCs and glycosaminoglycans and suggest that a dynamic shuffling of the HCs occur in vivo. |
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Keywords: | Extracellular Matrix/Hyaluronan Extracellular Matrix/Glycosaminoglycan Extracellular Matrix/Link Proteins Protein/Protein-Protein Interactions Proteoglycans Structure Enzyme Mechanisms Extracellular Matrix Extracellular Matrix Proteins |
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