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Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions
Published on: December 20, 2017
Cytoplasmic R-peptide of murine leukemia virus envelope protein negatively regulates its interaction with the cell
Yoshinao Kubo1, Mai Izumida2, Kei Togawa1
1Program for Nurturing Global Leaders in Tropical Medicine and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Abstract:
Cytoplasmic tails of envelope (Env) glycoproteins of many retroviruses inhibit their membrane fusion activity. The cytoplasmic 16-amino acid peptide of ecotropic murine leukemia virus (E-MLV) Env protein, called the R-peptide, also inhibits the membrane fusion activity of the Env protein. However, the molecular mechanism of the inhibition has not been elucidated yet. In this study, we found that R-peptide-containing Env protein of E-MLV binds to the cell surface receptor cationic amino acid transporter-1 (CAT-1) with weaker affinity than R-peptide-truncated Env protein. Consistent with this result, R-peptide-containing Env protein had less efficient inhibition of E-MLV vector infection than R-peptide-truncated Env protein. R-peptide truncation has been reported to induce conformational change in the surface subunit of E-MLV Env protein that interacts with the receptor. Taken together, our findings indicate that R-peptide truncation induces conformational change in the receptor-binding domain of the E-MLV Env protein and facilitates the Env-receptor interaction.
Insights
The R-peptide in ecotropic murine leukemia virus (E-MLV) Env protein inhibits fusion. Removing this R-peptide enhances Env-receptor binding and E-MLV infection.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Retroviral envelope (Env) glycoproteins mediate viral entry.
- Cytoplasmic tails of Env proteins can inhibit membrane fusion.
- The R-peptide of ecotropic murine leukemia virus (E-MLV) Env protein is known to inhibit fusion, but its mechanism is unclear.
Purpose of the Study:
- To elucidate the molecular mechanism by which the R-peptide of E-MLV Env protein inhibits membrane fusion.
- To investigate the effect of R-peptide truncation on Env-receptor interaction and viral infectivity.
Main Methods:
- Comparative analysis of Env-receptor binding affinity.
- Assessment of viral vector infection efficiency.
- Evaluation of conformational changes in the Env protein.
Main Results:
- E-MLV Env protein containing the R-peptide exhibited weaker binding affinity to the cationic amino acid transporter-1 (CAT-1) receptor compared to R-peptide-truncated Env.
- R-peptide-containing Env protein showed less efficient inhibition of E-MLV vector infection.
- R-peptide truncation was associated with conformational changes in the receptor-binding domain of the E-MLV Env protein.
Conclusions:
- The R-peptide of E-MLV Env protein inhibits Env-receptor interaction.
- R-peptide truncation induces conformational changes that facilitate Env-receptor binding.
- These findings provide insight into the regulation of retroviral membrane fusion and viral entry.
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