Transmembrane Peptides as a New Strategy to Inhibit Neuraminidase-1 Activation.
interfering peptides
membrane protein dimerization
neuraminidase-1
sialidase activity
transmembrane domain
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2020
2020
Historique:
received:
28
09
2020
accepted:
27
11
2020
entrez:
4
1
2021
pubmed:
5
1
2021
medline:
5
1
2021
Statut:
epublish
Résumé
Sialidases, or neuraminidases, are involved in several human disorders such as neurodegenerative, infectious and cardiovascular diseases, and cancers. Accumulative data have shown that inhibition of neuraminidases, such as NEU1 sialidase, may be a promising pharmacological target, and selective inhibitors of NEU1 are therefore needed to better understand the biological functions of this sialidase. In the present study, we designed interfering peptides (IntPep) that target a transmembrane dimerization interface previously identified in human NEU1 that controls its membrane dimerization and sialidase activity. Two complementary strategies were used to deliver the IntPep into cells, either flanked to a TAT sequence or non-tagged for solubilization in detergent micelles. Combined with molecular dynamics simulations and heteronuclear nuclear magnetic resonance (NMR) studies in membrane-mimicking environments, our results show that these IntPep are able to interact with the dimerization interface of human NEU1, to disrupt membrane NEU1 dimerization and to strongly decrease its sialidase activity at the plasma membrane. In conclusion, we report here new selective inhibitors of human NEU1 of strong interest to elucidate the biological functions of this sialidase.
Identifiants
pubmed: 33392200
doi: 10.3389/fcell.2020.611121
pmc: PMC7772355
doi:
Types de publication
Journal Article
Langues
eng
Pagination
611121Informations de copyright
Copyright © 2020 Albrecht, Kuznetsov, Appert-Collin, Dhaideh, Callewaert, Bershatsky, Urban, Bocharov, Bagnard, Baud, Blaise, Romier-Crouzet, Efremov, Dauchez, Duca, Gueroult, Maurice and Bennasroune.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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