Revising the mechanism of p75NTR activation: intrinsically monomeric state of death domains invokes the "helper" hypothesis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 08 2020
13 08 2020
Historique:
received:
22
04
2020
accepted:
27
07
2020
entrez:
15
8
2020
pubmed:
15
8
2020
medline:
12
1
2021
Statut:
epublish
Résumé
The neurotrophin receptor p75NTR plays crucial roles in neuron development and regulates important neuronal processes like degeneration, apoptosis and cell survival. At the same time the detailed mechanism of signal transduction is unclear. One of the main hypotheses known as the snail-tong mechanism assumes that in the inactive state, the death domains interact with each other and in response to ligand binding there is a conformational change leading to their exposure. Here, we show that neither rat nor human p75NTR death domains homodimerize in solution. Moreover, there is no interaction between the death domains in a more native context: the dimerization of transmembrane domains in liposomes and the presence of activating mutation in extracellular juxtamembrane region do not lead to intracellular domain interaction. These findings suggest that the activation mechanism of p75NTR should be revised. Thus, we propose a novel model of p75NTR functioning based on interaction with "helper" protein.
Identifiants
pubmed: 32792564
doi: 10.1038/s41598-020-70721-8
pii: 10.1038/s41598-020-70721-8
pmc: PMC7427093
doi:
Substances chimiques
Ligands
0
Liposomes
0
NGFR protein, human
0
Nerve Tissue Proteins
0
Receptors, Growth Factor
0
Receptors, Nerve Growth Factor
0
Ngfr protein, rat
136958-07-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13686Références
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