期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 41, 页码 29642-29653出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.477422
关键词
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资金
- German Federal Ministry of Education and Research [0315157]
- Spanish Ministry of Economy and Competitiveness [MAT2011-24306, RYC2009-04275]
- European Research Council [306435]
- Arthritis Research UK [18472, 19489]
- Medical Research Council [G0701180, G0800127]
- MRC [G0701180] Funding Source: UKRI
- Medical Research Council [G0701180] Funding Source: researchfish
- Versus Arthritis [18472, 19489] Funding Source: researchfish
Under inflammatory conditions and in the matrix of the cumulus-oocyte complex, the polysaccharide hyaluronan (HA) becomes decorated covalently with heavy chains (HCs) of the serum glycoprotein inter-alpha-inhibitor (I alpha I). This alters the functional properties of the HA as well as its structural role within extracellular matrices. The covalent transfer of HCs from I alpha I to HA is catalyzed by TSG-6 (tumor necrosis factor-stimulated gene-6), but TSG-6 is also known as a HA cross-linker that induces condensation of the HA matrix. Here, we investigate the interplay of these two distinct functions of TSG-6 by studying the ternary interactions of I alpha I and TSG-6 with well defined films of end-grafted HA chains. We demonstrate that TSG-6-mediated cross-linking of HA films is impaired in the presence of I alpha I and that this effect suppresses the TSG-6-mediated enhancement of HA binding to CD44-positive cells. Furthermore, we find that the interaction of TSG-6 and I alpha I in the presence of HA gives rise to two types of complexes that independently promote the covalent transfer of heavy chains to HA. One type of complex interacts very weakly with HA and is likely to correspond to the previously reported covalent HC.TSG-6 complexes. The other type of complex is novel and binds stably but noncovalently to HA. Prolonged incubation with TSG-6 and I alpha I leads toHA films that contain, in addition to covalently HA-bound HCs, several tightly but noncovalently bound molecular species. These findings have important implications for understanding how the biological activities of TSG-6 are regulated, such that the presence or absence of I alpha I will dictate its function.
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