Sanggaard Kristian W, Sonne-Schmidt Carsten S, Krogager Toke P, Lorentzen Karen A, Wisniewski Hans-Georg, Thøgersen Ida B, Enghild Jan J
Center for Insoluble Protein Structures (inSPIN) and Interdisciplinary Nanoscience Center (iNANO) at the Department of Molecular Biology, Science Park, University of Aarhus, Gustav Wiedsvej 10C, 8000 Aarhus C, Denmark.
J Biol Chem. 2008 Jul 4;283(27):18530-7. doi: 10.1074/jbc.M800874200. Epub 2008 Apr 29.
Tumor necrosis factor-stimulated gene-6 protein (TSG-6) is involved in the transfer of heavy chains (HCs) from inter-alpha-inhibitor (IalphaI), pre-alpha-inhibitor, and as shown here HC2.bikunin to hyaluronan through the formation of covalent HC.TSG-6 intermediates. In contrast to IalphaI and HC2.bikunin, pre-alpha-inhibitor does not form a covalent complex in vitro using purified proteins but needs the presence of another factor (Rugg, M. S., Willis, A. C., Mukhopadhyay, D., Hascall, V. C., Fries, E., Fülöp, C., Milner, C. M., and Day, A. J. (2005) J. Biol. Chem. 280, 25674-25686). In the present study we purified the required component from human plasma and identified it as HC2. Proteins containing HC2 including IalphaI, HC2.bikunin, and free HC2 promoted the formation of HC3.TSG-6 and subsequently HC3.hyaluronan complexes. HC1 or HC3 did not possess this activity. The presented data reveal that both HC2 and TSG-6 are required for the transesterification reactions to occur.
肿瘤坏死因子刺激基因6蛋白（TSG-6）通过形成共价的重链（HC）-TSG-6中间体，参与将重链从α-抑制因子（IαI）、前α-抑制因子以及本文所示的HC2-比昆宁转移至透明质酸。与IαI和HC2-比昆宁不同，前α-抑制因子在体外使用纯化蛋白时不会形成共价复合物，而是需要另一种因子的存在（Rugg, M. S., Willis, A. C., Mukhopadhyay, D., Hascall, V. C., Fries, E., Fülöp, C., Milner, C. M., and Day, A. J. (2005) J. Biol. Chem. 280, 25674-25686）。在本研究中，我们从人血浆中纯化了所需成分，并将其鉴定为HC2。含有HC2的蛋白质，包括IαI、HC2-比昆宁和游离的HC2，促进了HC3-TSG-6以及随后的HC3-透明质酸复合物的形成。HC1或HC3不具备这种活性。所呈现的数据表明，HC2和TSG-6都是发生酯交换反应所必需的。
