6NHY

Structure of the transmembrane domain of the Death Receptor 5 mutant (G217Y) - Trimer Only

6NHY の概要

• エントリーDOI: 10.2210/pdb6nhy/pdb
• NMR情報: BMRB: 30554
• 分子名称: Tumor necrosis factor receptor superfamily member 10B (1 entity in total)
• 機能のキーワード: transmembrane helix trimer, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 11495.46

構造登録者

Chou, J.J.,Pan, L.,Zhao, L.,Chen, W.,Piai, A.,Fu, T.,Wu, H.,Liu, Z. (登録日: 2018-12-24, 公開日: 2019-02-27, 最終更新日: 2024-05-15)

主引用文献

Pan, L.,Fu, T.M.,Zhao, W.,Zhao, L.,Chen, W.,Qiu, C.,Liu, W.,Liu, Z.,Piai, A.,Fu, Q.,Chen, S.,Wu, H.,Chou, J.J.
Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling.
Cell, 176:1477-1489.e14, 2019

PubMed Abstract: Receptor clustering on the cell membrane is critical in the signaling of many immunoreceptors, and this mechanism has previously been attributed to the extracellular and/or the intracellular interactions. Here, we report an unexpected finding that for death receptor 5 (DR5), a receptor in the tumor necrosis factor receptor superfamily, the transmembrane helix (TMH) alone in the receptor directly assembles a higher-order structure to drive signaling and that this structure is inhibited by the unliganded ectodomain. Nuclear magnetic resonance structure of the TMH in bicelles shows distinct trimerization and dimerization faces, allowing formation of dimer-trimer interaction networks. Single-TMH mutations that disrupt either trimerization or dimerization abolish ligand-induced receptor activation. Surprisingly, proteolytic removal of the DR5 ectodomain can fully activate downstream signaling in the absence of ligand. Our data suggest a receptor activation mechanism in which binding of ligand or antibodies to overcome the pre-ligand autoinhibition allows TMH clustering and thus signaling.

PubMed: 30827683
DOI: 10.1016/j.cell.2019.02.001

実験手法

SOLUTION NMR