Drosophila TNFRs Grindelwald and Wengen bind Eiger with different affinities and promote distinct cellular functions
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- Drosophila TNFRs Grindelwald and Wengen bind Eiger with different affinities and promote distinct cellular functions
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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.
Original language | English |
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Article number | 2070 |
Journal | Nature Communications |
Volume | 12 |
Number of pages | 12 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2021 |
- Amino Acid Sequence, Animals, Apoptosis, Cytoplasmic Vesicles/metabolism, Drosophila Proteins/chemistry, Drosophila melanogaster/cytology, Endocytosis, Imaginal Discs/cytology, Membrane Proteins/chemistry, Protein Binding, Protein Domains, Protein Interaction Mapping, Receptors, Tumor Necrosis Factor/metabolism
Research areas
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