2WNO

X-ray Structure of CUB_C domain from TSG-6

2WNO の概要

• エントリーDOI: 10.2210/pdb2wno/pdb
• 関連するPDBエントリー: 1O7B 1O7C 2PF5
• 分子名称: TUMOR NECROSIS FACTOR-INDUCIBLE GENE 6 PROTEIN, COBALT (II) ION, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: glycoprotein, cell adhesion, extracellular matrix
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16766.47

構造登録者

Briggs, D.C.,Day, A.J. (登録日: 2009-07-13, 公開日: 2010-09-01, 最終更新日: 2024-11-06)

主引用文献

Briggs, D.C.,Birchenough, H.L.,Ali, T.,Rugg, M.S.,Waltho, J.P.,Ievoli, E.,Jowitt, T.A.,Enghild, J.J.,Richter, R.P.,Salustri, A.,Milner, C.M.,Day, A.J.
Metal Ion-Dependent Heavy Chain Transfer Activity of Tsg-6 Mediates Assembly of the Cumulus-Oocyte Matrix.
J.Biol.Chem., 290:28708-, 2015

PubMed 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.

PubMed: 26468290
DOI: 10.1074/JBC.M115.669838

実験手法

X-RAY DIFFRACTION (2.3 Å)