3ZJB

The structure of the TRAF domain of human TRAF4

3ZJB の概要

• エントリーDOI: 10.2210/pdb3zjb/pdb
• 分子名称: TNF RECEPTOR-ASSOCIATED FACTOR 4, CHLORIDE ION (3 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q9BUZ4
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 68289.52

構造登録者

McEwen, A.G.,Poussin-Courmontagne, P.,Rousseau, A.,Rogna, D.,Nomine, Y.,Rio, M.-C.,Tomasetto, C.,Alpy, F. (登録日: 2013-01-17, 公開日: 2013-12-04, 最終更新日: 2023-12-20)

主引用文献

Rousseau, A.,Mcewen, A.G.,Poussin-Courmontagne, P.,Rognan, D.,Nomine, Y.,Rio, M.-C.,Tomasetto, C.,Alpy, F.
Traf4 is a Novel Phosphoinositide-Binding Protein Modulating Tight Junctions and Favoring Cell Migration.
Plos Biol., 11:1726-, 2013

PubMed Abstract: Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.

PubMed: 24311986
DOI: 10.1371/JOURNAL.PBIO.1001726

実験手法

X-RAY DIFFRACTION (1.84 Å)