Role of Amphipathic Helix of a Herpesviral Protein in Membrane Deformation and T Cell Receptor Downregulation
2008

Role of Amphipathic Helix of a Herpesviral Protein in Membrane Deformation and T Cell Receptor Downregulation

publication Evidence: high

Author Information

Author(s): Min Chan-Ki, Bang Sun-Young, Cho Bon-A, Choi Yun-Hui, Yang Jae-Seong, Lee Sun-Hwa, Seong Seung-Yong, Kim Ki Woo, Kim Sanguk, Jung Jae Ung, Choi Myung-Sik, Kim Ik-Sang, Cho Nam-Hyuk

Primary Institution: Seoul National University Medical Research Center and Bundang Hospital, Seoul, Korea

Hypothesis

The membrane-proximal amphipathic helix of the herpesviral protein Tip mediates lipid raft localization and membrane deformation.

Conclusion

The amphipathic helix of Tip is essential for its localization in lipid rafts and for the selective downregulation of T cell receptors.

Supporting Evidence

  • The amphipathic helix binds to negatively charged lipids and induces liposome tubulation.
  • Tip's amphipathic helix is required for efficient localization in lipid rafts.
  • Mutations in the amphipathic helix impair TCR/CD3 downregulation.
  • Tip's TM domain is necessary for oligomerization and lysosomal trafficking.
  • Tip interacts with Lck and p80 to facilitate receptor downregulation.

Takeaway

This study found that a part of a virus protein helps it change cell membranes and lower the number of certain receptors on T cells, which could help the virus stay in the body longer.

Methodology

The study involved mutagenesis analysis, flow cytometry, and confocal microscopy to assess the role of the amphipathic helix in lipid raft localization and receptor downregulation.

Digital Object Identifier (DOI)

10.1371/journal.ppat.1000209

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