{"title":"The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers","quality_controlled":"1","author":[{"id":"38661662-F248-11E8-B48F-1D18A9856A87","last_name":"Baranova","orcid":"0000-0002-3086-9124","first_name":"Natalia","full_name":"Baranova, Natalia"},{"last_name":"Nilebäck","first_name":"Erik","full_name":"Nilebäck, Erik"},{"first_name":"F. Michael","full_name":"Haller, F. Michael","last_name":"Haller"},{"last_name":"Briggs","full_name":"Briggs, David C.","first_name":"David C."},{"last_name":"Svedhem","first_name":"Sofia","full_name":"Svedhem, Sofia"},{"last_name":"Day","first_name":"Anthony J.","full_name":"Day, Anthony J."},{"first_name":"Ralf P.","full_name":"Richter, Ralf P.","last_name":"Richter"}],"doi":"10.1074/jbc.m111.247395","_id":"6298","main_file_link":[{"url":"http://www.jbc.org/content/286/29/25675.full.pdf","open_access":"1"}],"oa_version":"Published Version","abstract":[{"text":"Tumor necrosis factor-stimulated gene-6 (TSG-6) is a hyalu-ronan (HA)-binding protein that plays important roles ininflammation and ovulation. TSG-6-mediated cross-linking ofHA has been proposed as a functional mechanism (e.g.for regu-lating leukocyte adhesion), but direct evidence for cross-linkingis lacking, and we know very little about its impact on HA ultra-structure. Here we used films of polymeric and oligomeric HAchains, end-grafted to a solid support, and a combination ofsurface-sensitive biophysical techniques to quantify the bindingof TSG-6 into HA films and to correlate binding to morpholog-ical changes. We find that full-length TSG-6 binds with pro-nounced positive cooperativity and demonstrate that it cancross-link HA at physiologically relevant concentrations. Ourdata indicate that cooperative binding of full-length TSG-6arises from HA-induced protein oligomerization and that theTSG-6 oligomers act as cross-linkers. In contrast, the HA-bind-ing domain of TSG-6 (the Link module) alone binds withoutpositive cooperativity and weaker than the full-length protein.Both the Link module and full-length TSG-6 condensed andrigidified HA films, and the degree of condensation scaled withthe affinity between the TSG-6 constructs and HA. We proposethat condensation is the result of protein-mediated HA cross-linking. Our findings firmly establish that TSG-6 is a potent HAcross-linking agent and might hence have important implica-tions for the mechanistic understanding of the biological func-tion of TSG-6 (e.g.in inflammation).","lang":"eng"}],"publication_status":"published","publication":"Journal of Biological Chemistry","issue":"29","type":"journal_article","extern":"1","volume":286,"date_updated":"2021-01-12T08:06:58Z","language":[{"iso":"eng"}],"intvolume":"       286","publication_identifier":{"issn":["0021-9258","1083-351X"]},"day":"22","page":"25675-25686","year":"2011","status":"public","publisher":"American Society for Biochemistry & Molecular Biology","oa":1,"date_published":"2011-07-22T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2019-04-11T20:57:43Z","month":"07","citation":{"mla":"Baranova, Natalia S., et al. “The Inflammation-Associated Protein TSG-6 Cross-Links Hyaluronan via Hyaluronan-Induced TSG-6 Oligomers.” <i>Journal of Biological Chemistry</i>, vol. 286, no. 29, American Society for Biochemistry &#38; Molecular Biology, 2011, pp. 25675–86, doi:<a href=\"https://doi.org/10.1074/jbc.m111.247395\">10.1074/jbc.m111.247395</a>.","ama":"Baranova NS, Nilebäck E, Haller FM, et al. The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. <i>Journal of Biological Chemistry</i>. 2011;286(29):25675-25686. doi:<a href=\"https://doi.org/10.1074/jbc.m111.247395\">10.1074/jbc.m111.247395</a>","short":"N.S. Baranova, E. Nilebäck, F.M. Haller, D.C. Briggs, S. Svedhem, A.J. Day, R.P. Richter, Journal of Biological Chemistry 286 (2011) 25675–25686.","ieee":"N. S. Baranova <i>et al.</i>, “The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers,” <i>Journal of Biological Chemistry</i>, vol. 286, no. 29. American Society for Biochemistry &#38; Molecular Biology, pp. 25675–25686, 2011.","chicago":"Baranova, Natalia S., Erik Nilebäck, F. Michael Haller, David C. Briggs, Sofia Svedhem, Anthony J. Day, and Ralf P. Richter. “The Inflammation-Associated Protein TSG-6 Cross-Links Hyaluronan via Hyaluronan-Induced TSG-6 Oligomers.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology, 2011. <a href=\"https://doi.org/10.1074/jbc.m111.247395\">https://doi.org/10.1074/jbc.m111.247395</a>.","ista":"Baranova NS, Nilebäck E, Haller FM, Briggs DC, Svedhem S, Day AJ, Richter RP. 2011. The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. Journal of Biological Chemistry. 286(29), 25675–25686.","apa":"Baranova, N. S., Nilebäck, E., Haller, F. M., Briggs, D. C., Svedhem, S., Day, A. J., &#38; Richter, R. P. (2011). The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.m111.247395\">https://doi.org/10.1074/jbc.m111.247395</a>"}}