TY - JOUR AU1 - Sanggaard, Kristian W. AU2 - Karring, Henrik AU3 - Valnickova, Zuzana AU4 - Thøgersen, Ida B. AU5 - Enghild, Jan J. AB -

During co-incubation of human inter-α-inhibitor (IαI) and human tumor necrosis factor-stimulated gene 6 protein (TSG-6) SDS-stable interactions are formed between the two proteins. We have analyzed the products of this reaction and characterized the mechanism of complex formation. Following the incubation seven new bands not previously identified were apparent in SDS-PAGE. Three of these bands did not contain TSG-6, including heavy chain (HC)1·bikunin, HC2·bikunin, and free bikunin. In addition high molecular weight complexes composed of the same components as IαI, including HC1, HC2, and bikunin, were formed. The formation of these complexes was prevented by the addition of hyaluronan. The cross-links stabilizing these complexes displaying properties similar to the protein-glycosaminoglycan-protein (PGP) cross-link. The TSG-6-containing SDS-stable complexes were composed of HC1·TSG-6 or HC2·TSG-6 exclusively. Both glycosylated and non-glycosylated TSG-6 participated in the complex formation. The HC·TSG-6 cross-links were different from the PGP cross-link and were determined to be ester bonds between the α-carbonyl of the C-terminal Asp of the heavy chain and most likely a hydroxyl group containing the TSG-6 residue. The mechanism involved cleaving the PGP cross-link of IαI during a transesterification reaction. A TSG-6 hydroxyl group reacts with the ester bond between the α-carbonyl of the C-terminal Asp residues of HC1 or HC2 and carbon-6 of an internal N-acetylgalactosamine of the chondroitin-4-sulfate chain. An intermediate is formed resulting in a partitioning of the reaction between HC(1 or 2)·TSG-6 complexes and transfer of HC(1 or 2) to the chondroitin via competing pathways.

TI - The TSG-6 and IαI Interaction Promotes a Transesterification Cleaving the Protein-Glycosaminoglycan-Protein (PGP) Cross-link * [boxs] JF - Journal of Biological Chemistry DO - 10.1074/jbc.m409016200 DA - 2005-03-25 UR - https://www.deepdyve.com/lp/american-society-for-biochemistry-and-molecular-biology/the-tsg-6-and-i-i-interaction-promotes-a-transesterification-cleaving-qFs5t05Fl9 SP - 11936 EP - 11942 VL - 280 IS - 12 DP - DeepDyve ER -