MeCP2 is a naturally supercharged protein with cell membrane transduction capabilities.
MeCP2
TAT fusion proteins
cell penetrating peptides
supercharged protein
Journal
Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750
Informations de publication
Date de publication:
Oct 2024
Oct 2024
Historique:
revised:
23
08
2024
received:
24
04
2024
accepted:
26
08
2024
medline:
14
9
2024
pubmed:
14
9
2024
entrez:
14
9
2024
Statut:
ppublish
Résumé
The intrinsically disordered protein MeCP2 is a global transcriptional regulator encoded by the MECP2 gene. Although the structured domains of MeCP2 have been the subject of multiple studies, its unstructured regions have not been that extensively characterized. In this work, we show that MeCP2 possesses properties akin to those of supercharged proteins. By utilizing its unstructured portions, MeCP2 can successfully transduce across cell membranes and localize to heterochromatic foci in the nuclei, displaying uptake levels a third lower than a MeCP2 construct fused to the cell-penetrating peptide TAT. MeCP2 uptake can further be enhanced by the addition of compounds that promote endosomal escape following cellular trafficking by means of macropinocytosis. Using a combination of in silico prediction algorithms and live-cell imaging experiments, we mapped the sequence in MeCP2 responsible for its cellular incorporation, which bears a striking resemblance to TAT itself. Transduced MeCP2 was shown to interact with HDAC3. These findings provide valuable insight into the properties of MeCP2 and may be beneficial for devising future protein-based treatment strategies.
Substances chimiques
Methyl-CpG-Binding Protein 2
0
Histone Deacetylases
EC 3.5.1.98
MECP2 protein, human
0
histone deacetylase 3
EC 3.5.1.98
Cell-Penetrating Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e5170Subventions
Organisme : Italian Rett Syndrome Association
Informations de copyright
© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
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