6ZSY

Crystal structure of the Grindelwald extracellular domain complex

6ZSY の概要

• エントリーDOI: 10.2210/pdb6zsy/pdb
• 分子名称: Protein grindelwald (2 entities in total)
• 機能のキーワード: tnf receptor, jnk cascade, tnf, signaling, extracellular, tumor necrosis factor, signaling protein
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5919.62

構造登録者

Palmerini, V.,Cecatiello, V.,Pasqualato, S.,Mapelli, M. (登録日: 2020-07-17, 公開日: 2021-03-31, 最終更新日: 2024-11-13)

主引用文献

Palmerini, V.,Monzani, S.,Laurichesse, Q.,Loudhaief, R.,Mari, S.,Cecatiello, V.,Olieric, V.,Pasqualato, S.,Colombani, J.,Andersen, D.S.,Mapelli, M.
Drosophila TNFRs Grindelwald and Wengen bind Eiger with different affinities and promote distinct cellular functions.
Nat Commun, 12:2070-2070, 2021

PubMed Abstract: The Drosophila tumour necrosis factor (TNF) ligand-receptor system consists of a unique ligand, Eiger (Egr), and two receptors, Grindelwald (Grnd) and Wengen (Wgn), and therefore provides a simple system for exploring the interplay between ligand and receptors, and the requirement for Grnd and Wgn in TNF/Egr-mediated processes. Here, we report the crystallographic structure of the extracellular domain (ECD) of Grnd in complex with Egr, a high-affinity hetero-hexameric assembly reminiscent of human TNF:TNFR complexes. We show that ectopic expression of Egr results in internalisation of Egr:Grnd complexes in vesicles, a step preceding and strictly required for Egr-induced apoptosis. We further demonstrate that Wgn binds Egr with much reduced affinity and is localised in intracellular vesicles that are distinct from those containing Egr:Grnd complexes. Altogether, our data provide insight into ligand-mediated activation of Grnd and suggest that distinct affinities of TNF ligands for their receptors promote different and non-redundant cellular functions.

PubMed: 33824334
DOI: 10.1038/s41467-021-22080-9

実験手法

X-RAY DIFFRACTION (0.926 Å)