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. / Palmerini, Valentina; Monzani, Silvia; Laurichesse, Quentin; Loudhaief, Rihab; Mari, Sara; Cecatiello, Valentina; Olieric, Vincent; Pasqualato, Sebastiano; Colombani, Julien; Andersen, Ditte S; Mapelli, Marina.
In: Nature Communications, Vol. 12, 2070, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Drosophila TNFRs Grindelwald and Wengen bind Eiger with different affinities and promote distinct cellular functions
AU - Palmerini, Valentina
AU - Monzani, Silvia
AU - Laurichesse, Quentin
AU - Loudhaief, Rihab
AU - Mari, Sara
AU - Cecatiello, Valentina
AU - Olieric, Vincent
AU - Pasqualato, Sebastiano
AU - Colombani, Julien
AU - Andersen, Ditte S
AU - Mapelli, Marina
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Animals
KW - Apoptosis
KW - Cytoplasmic Vesicles/metabolism
KW - Drosophila Proteins/chemistry
KW - Drosophila melanogaster/cytology
KW - Endocytosis
KW - Imaginal Discs/cytology
KW - Membrane Proteins/chemistry
KW - Protein Binding
KW - Protein Domains
KW - Protein Interaction Mapping
KW - Receptors, Tumor Necrosis Factor/metabolism
U2 - 10.1038/s41467-021-22080-9
DO - 10.1038/s41467-021-22080-9
M3 - Journal article
C2 - 33824334
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2070
ER -
ID: 260041345