Mutational analysis of hepatitis B virus pre-S1 (9-24) fusogenic peptide.
Biochem Biophys Res Commun
; 474(2): 406-412, 2016 05 27.
Article
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| MEDLINE
| ID: mdl-27120459
ABSTRACT
A hollow nanoparticle known as a bio-nanocapsule (BNC) consisting of hepatitis B virus (HBV) envelope L protein and liposome (LP) can encapsulate drugs and genes and thereby deliver them in vitro and in vivo to human hepatic tissues, specifically by utilizing the HBV-derived infection machinery. Recently, we identified a low pH-dependent fusogenic domain at the N-terminal part of the pre-S1 region of the HBV L protein (amino acid residues 9 to 24; NPLGFFPDHQLDPAFG), which shows membrane destabilizing activity (i.e., membrane fusion, membrane disruption, and payload release) upon interaction with target LPs. In this study, instead of BNC and HBV, we generated LPs displaying a mutated form of the pre-S1 (9-24) peptide, and performed a membrane disruption assay using target LPs containing pyranine (fluorophore) and p-xylene-bis (N-pyridinium bromide) (DPX) as a quencher. The membrane disruption activity was found to correlate with the hydrophobicity of the whole structure, while the peptide retained a random-coil structure even under low pH condition. One large hydrophobic cluster (I) and one small hydrophobic cluster (II) residing in the peptide would be connected by the protonation of residues D16 and D20, and thereby exhibit strong membrane disruption activity in a low pH-dependent manner. Furthermore, the introduction of a positively charged residue enhanced the activity significantly, suggesting that a sole positively charged residue (H17) may be important for the interaction with target LPs by electrostatic interaction. Collectively, these results suggest that the pre-S1 (9-24) peptide may be involved in the endosomal escape of the BNC's payloads, as well as in the HBV uncoating process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Precursores de Proteínas
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Análisis Mutacional de ADN
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Membrana Celular
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Virus de la Hepatitis B
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Antígenos de Superficie de la Hepatitis B
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Mutación
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2016
Tipo del documento:
Article
País de afiliación:
Japón