3KNV

Crystal structure of the RING and first zinc finger domains of TRAF2

3KNV の概要

• エントリーDOI: 10.2210/pdb3knv/pdb
• 関連するPDBエントリー: 3HCS
• 分子名称: TNF receptor-associated factor 2, ZINC ION (3 entities in total)
• 機能のキーワード: cross-brace, alternative splicing, apoptosis, cytoplasm, metal-binding, ubl conjugation, zinc, zinc-finger, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q12933
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15601.81

構造登録者

Yin, Q.,Wu, H. (登録日: 2009-11-12, 公開日: 2009-11-24, 最終更新日: 2024-02-21)

主引用文献

Yin, Q.,Lamothe, B.,Darnay, B.G.,Wu, H.
Structural basis for the lack of E2 interaction in the RING domain of TRAF2.
Biochemistry, 48:10558-10567, 2009

PubMed Abstract: TRAF proteins are intracellular signal transducers for a number of immune receptor superfamilies. Specifically, TRAF2 interacts with members of the TNF receptor superfamily and connects the receptors to downstream signaling proteins. It has been assumed that TRAF2 is a ubiquitin ligase like TRAF6 and mediates K63-linked polyubiquitination of RIP1, a kinase pivotal in TNFalpha-induced NF-kappaB activation. Here we report the crystal structure of the RING and the first zinc finger domains of TRAF2. We show that the TRAF2 RING structure is very different from the known TRAF6 RING structure. The differences are multifaceted, including amino acid differences at the critical Ubc13-interacting site, local conformational differences, and a unique nine-residue insertion between the RING domain and the first zinc finger in TRAF2. These structural differences prevent TRAF2 from interacting with Ubc13 and other related E2s via steric clash and unfavorable interfaces. Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling.

PubMed: 19810754
DOI: 10.1021/bi901462e

実験手法

X-RAY DIFFRACTION (1.9 Å)