1LB6

TRAF6-CD40 Complex

1LB6 の概要

• エントリーDOI: 10.2210/pdb1lb6/pdb
• 関連するPDBエントリー: 1LB4 1LB5
• 分子名称: TNF receptor-associated factor 6, CD40 antigen (3 entities in total)
• 機能のキーワード: traf6-cd40 complex, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : Q9Y4K3; Isoform I: Cell membrane; Single-pass type I membrane protein. Isoform II: Secreted: P25942
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19810.76

構造登録者

Ye, H.,Arron, J.R.,Lamothe, B.,Cirilli, M.,Kobayashi, T.,Shevde, N.K.,Segal, D.,Dzivenu, O.,Vologodskaia, M.,Yim, M.,Du, K.,Singh, S.,Pike, J.W.,Darnay, B.G.,Choi, Y.,Wu, H. (登録日: 2002-04-02, 公開日: 2002-07-31, 最終更新日: 2024-04-03)

主引用文献

Ye, H.,Arron, J.R.,Lamothe, B.,Cirilli, M.,Kobayashi, T.,Shevde, N.K.,Segal, D.,Dzivenu, O.K.,Vologodskaia, M.,Yim, M.,Du, K.,Singh, S.,Pike, J.W.,Darnay, B.G.,Choi, Y.,Wu, H.
Distinct molecular mechanism for initiating TRAF6 signalling.
Nature, 418:443-447, 2002

PubMed Abstract: Tumour-necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is the only TRAF family member that participates in signal transduction of both the TNF receptor (TNFR) superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily; it is important for adaptive immunity, innate immunity and bone homeostasis. Here we report crystal structures of TRAF6, alone and in complex with TRAF6-binding peptides from CD40 and TRANCE-R (also known as RANK), members of the TNFR superfamily, to gain insight into the mechanism by which TRAF6 mediates several signalling cascades. A 40 degrees difference in the directions of the bound peptides in TRAF6 and TRAF2 shows that there are marked structural differences between receptor recognition by TRAF6 and other TRAFs. The structural determinant of the petide TRAF6 interaction reveals a Pro-X-Glu-X-X-(aromatic/acidic residue) TRAF6-binding motif, which is present not only in CD40 and TRANCE-R but also in the three IRAK adapter kinases for IL-1R/TLR signalling. Cell-permeable peptides with the TRAF6-binding motif inhibit TRAF6 signalling, which indicates their potential as therapeutic modulators. Our studies identify a universal mechanism by which TRAF6 regulates several signalling cascades in adaptive immunity, innate immunity and bone homeostasis.

PubMed: 12140561
DOI: 10.1038/nature00888

実験手法

X-RAY DIFFRACTION (1.8 Å)