ArticleThe Journal of biological chemistry2015
Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Proprotein convertase activity regulates cumulus-oocyte-complex matrix integrity and cumulus cell migration during ovulation via a GDF9-dependent mechanism.bioRxiv : the preprint server for biology · 2026Article
- Chemical modification of hyaluronan oligosaccharides differentially modulates hyaluronan-hyaladherin interactions.The Journal of biological chemistry · 2024Article
- Biomimetic Hyaluronan Binding Biomaterials to Capture the Complex Regulation of Hyaluronan in Tissue Development and Function.Biomimetics (Basel, Switzerland) · 2024Review
- Review
- Endogenous TSG-6 modulates corneal inflammation following chemical injury.The ocular surface · 2024Article
- Inter-alpha-trypsin inhibitor (IαI) and hyaluronan modifications enhance the innate immune response to influenza virus in the lung.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores.Analytical chemistry · 2024Article
- TSG6 hyaluronan matrix remodeling dampens the inflammatory response during colitis.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- ATAC-seq and RNA-seq analysis unravel the mechanism of sex differentiation and infertility in sex reversal chicken.Epigenetics & chromatin · 2023Article
- Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn's Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal Transition.Cellular and molecular gastroenterology and hepatology · 2023Article
- Extracellular matrix-derived scaffolds in constructing artificial ovaries for ovarian failure: a systematic methodological review.Human reproduction open · 2023Review
- Noncovalent hyaluronan crosslinking by TSG-6: Modulation by heparin, heparan sulfate, and PRG4.Frontiers in molecular biosciences · 2022Article
- Synapse Formation and Function Across Species: Ancient Roles for CCP, CUB, and TSP-1 Structural Domains.Frontiers in neuroscience · 2022Review
- Kainate receptor modulation by NETO2.Nature · 2021Article
- Evolutionary, proteomic, and experimental investigations suggest the extracellular matrix of cumulus cells mediates fertilization outcomes†.Biology of reproduction · 2021Article
- A Personal Tribute to Robert B. Sim with Reflections on Our Work Together on Factor H.Viruses · 2021Article
- The Inter-α-Trypsin Inhibitor Family: Versatile Molecules in Biology and Pathology.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- [Research progress on the role of pentraxin 3 in polycystic ovary syndrome].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Article
- TSG-6 Is Weakly Chondroprotective in Murine OA but Does not Account for FGF2-Mediated Joint Protection.ACR open rheumatology · 2020Article
- Inter-α-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation.The Journal of biological chemistry · 2020Article
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Authors and funding
12 authors at 6 institutions in 6 countries.
Funding
Abstract
The matrix polysaccharide hyaluronan (HA) has a critical role in the expansion of the cumulus cell-oocyte complex (COC), a process that is necessary for ovulation and fertilization in most mammals. Hyaluronan is organized into a cross-linked network by the cooperative action of three proteins, inter-α-inhibitor (IαI), pentraxin-3, and TNF-stimulated gene-6 (TSG-6), driving the expansion of the COC and providing the cumulus matrix with its required viscoelastic properties. Although it is known that matrix stabilization involves the TSG-6-mediated transfer of IαI heavy chains (HCs) onto hyaluronan (to form covalent HC·HA complexes that are cross-linked by pentraxin-3) and that this occurs via the formation of covalent HC·TSG-6 intermediates, the underlying molecular mechanisms are not well understood. Here, we have determined the tertiary structure of the CUB module from human TSG-6, identifying a calcium ion-binding site and chelating glutamic acid residue that mediate the formation of HC·TSG-6. This occurs via an initial metal ion-dependent, non-covalent, interaction between TSG-6 and HCs that also requires the presence of an HC-associated magnesium ion. In addition, we have found that the well characterized hyaluronan-binding site in the TSG-6 Link module is not used for recognition during transfer of HCs onto HA. Analysis of TSG-6 mutants (with impaired transferase and/or hyaluronan-binding functions) revealed that although the TSG-6-mediated formation of HC·HA complexes is essential for the expansion of mouse COCs in vitro, the hyaluronan-binding function of TSG-6 does not play a major role in the stabilization of the murine cumulus matrix.
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