2N97

DD homodimer

2N97 の概要

• エントリーDOI: 10.2210/pdb2n97/pdb
• 関連するPDBエントリー: 2N7Z 2N80 2N83
• NMR情報: BMRB: 25883
• 分子名称: Tumor necrosis factor receptor superfamily member 16 (1 entity in total)
• 機能のキーワード: death domain, p75ntr, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P08138
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21061.40

構造登録者

Lin, Z.,Ibanez, C.F. (登録日: 2015-11-07, 公開日: 2015-12-23, 最終更新日: 2024-05-15)

主引用文献

Lin, Z.,Tann, J.Y.,Goh, E.T.,Kelly, C.,Lim, K.B.,Gao, J.F.,Ibanez, C.F.
Structural basis of death domain signaling in the p75 neurotrophin receptor
Elife, 4:11692-11692, 2015

PubMed Abstract: Death domains (DDs) mediate assembly of oligomeric complexes for activation of downstream signaling pathways through incompletely understood mechanisms. Here we report structures of complexes formed by the DD of p75 neurotrophin receptor (p75(NTR)) with RhoGDI, for activation of the RhoA pathway, with caspase recruitment domain (CARD) of RIP2 kinase, for activation of the NF-kB pathway, and with itself, revealing how DD dimerization controls access of intracellular effectors to the receptor. RIP2 CARD and RhoGDI bind to p75(NTR) DD at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding. The p75(NTR) DD forms non-covalent, low-affinity symmetric dimers in solution. The dimer interface overlaps with RIP2 CARD but not RhoGDI binding sites, supporting a model of receptor activation triggered by separation of DDs. These structures reveal how competitive protein-protein interactions orchestrate the hierarchical activation of downstream pathways in non-catalytic receptors.

PubMed: 26646181
DOI: 10.7554/eLife.11692

実験手法

SOLUTION NMR