Glycobiology and Extracellular Matrices
Inter-α-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation
Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis.Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix
Background: TSG-6 (TNF-stimulated gene-6)-dependent transfer of heavy chains from inter-α-inhibitor onto hyaluronan is critical for ovulation.Results: A calcium ion and chelating glutamate within TSG-6 mediate formation of the covalent heavy chain-TSG-6 intermediate.Conclusion: TSG-6 transferase activity rather than hyaluronan binding drives cumulus expansion.Significance: The role of metal ions in hyaluronan-heavy chain formation has been determined.
