The transfer of heavy chains from bikunin proteins to hyaluronan requires both TSG-6 and HC2.
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.
Sanggaard
Kristian W
KW
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.
Sonne-Schmidt
Carsten S
CS
Krogager
Toke P
TP
Lorentzen
Karen A
KA
Wisniewski
Hans-Georg
HG
Thøgersen
Ida B
IB
Enghild
Jan J
JJ
D000510:Alpha-Globulins / Q000737:chemistry* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism
D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; D046912:Multiprotein Complexes; C072273:TNFAIP6 protein, human; C016001:alpha-1-microglobulin; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid