4MXW

Structure of heterotrimeric lymphotoxin LTa1b2 bound to lymphotoxin beta receptor LTbR and anti-LTa Fab

4MXW の概要

• エントリーDOI: 10.2210/pdb4mxw/pdb
• 関連するPDBエントリー: 4MXV
• 分子名称: Tumor necrosis factor receptor superfamily member 3, Lymphotoxin-alpha, Lymphotoxin-beta, ... (5 entities in total)
• 機能のキーワード: tnf, tumor necrosis factor, tnfr receptor, lymphotoxin beta receptor, lymphotoxin alpha, lymphoid development, tumor immunity, auto-immunity, cytokine-immune system complex, cytokine/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P36941; Secreted: P01374; Membrane; Single-pass type II membrane protein (Potential): Q06643
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 259331.18

構造登録者

Sudhamsu, J.,Yin, J.P.,Hymowitz, S.G. (登録日: 2013-09-26, 公開日: 2013-11-13, 最終更新日: 2024-11-20)

主引用文献

Sudhamsu, J.,Yin, J.,Chiang, E.Y.,Starovasnik, M.A.,Grogan, J.L.,Hymowitz, S.G.
Dimerization of LT beta R by LT alpha 1 beta 2 is necessary and sufficient for signal transduction.
Proc.Natl.Acad.Sci.USA, 110:19896-19901, 2013

PubMed Abstract: Homotrimeric TNF superfamily ligands signal by inducing trimers of their cognate receptors. As a biologically active heterotrimer, Lymphotoxin(LT)α1β2 is unique in the TNF superfamily. How the three unique potential receptor-binding interfaces in LTα1β2 trigger signaling via LTβ Receptor (LTβR) resulting in lymphoid organogenesis and propagation of inflammatory signals is poorly understood. Here we show that LTα1β2 possesses two binding sites for LTβR with distinct affinities and that dimerization of LTβR by LTα1β2 is necessary and sufficient for signal transduction. The crystal structure of a complex formed by LTα1β2, LTβR, and the fab fragment of an antibody that blocks LTβR activation reveals the lower affinity receptor-binding site. Mutations targeting each potential receptor-binding site in an engineered single-chain variant of LTα1β2 reveal the high-affinity site. NF-κB reporter assays further validate that disruption of receptor interactions at either site is sufficient to prevent signaling via LTβR.

PubMed: 24248355
DOI: 10.1073/pnas.1310838110

実験手法

X-RAY DIFFRACTION (3.6 Å)