2wno
X-ray Structure of CUB_C domain from TSG-6
Structural highlights
FunctionTSG6_HUMAN Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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-alpha-inhibitor (IalphaI), 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 IalphaI 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. Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix.,Briggs DC, Birchenough HL, Ali T, Rugg MS, Waltho JP, Ievoli E, Jowitt TA, Enghild JJ, Richter RP, Salustri A, Milner CM, Day AJ J Biol Chem. 2015 Nov 27;290(48):28708-23. doi: 10.1074/jbc.M115.669838. Epub, 2015 Oct 14. PMID:26468290[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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