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http://purl.uniprot.org/citations/26468290http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26468290http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26468290http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m115.669838"xsd:string
http://purl.uniprot.org/citations/26468290http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m115.669838"xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Waltho J.P."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Waltho J.P."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Enghild J.J."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Enghild J.J."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Briggs D.C."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Briggs D.C."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Jowitt T.A."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Jowitt T.A."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Day A.J."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Day A.J."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Milner C.M."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Milner C.M."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Rugg M.S."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Rugg M.S."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Ali T."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Ali T."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Salustri A."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Salustri A."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Birchenough H.L."xsd:string
http://purl.uniprot.org/citations/26468290http://purl.uniprot.org/core/author"Birchenough H.L."xsd:string