Role of amphipathic helix of a herpesviral protein in membrane deformation and T cell receptor downregulation

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

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23 Scopus citations

Abstract

Lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. Tyrosine kinase interacting protein (Tip) of T lymphotropic Herpesvirus saimiri (HVS) is targeted to lipid rafts in T cells and downregulates TCR and CD4 surface expression. Here, we report that the membrane-proximal amphipathic helix preceding Tip's transmembrane (TM) domain mediates lipid raft localization and membrane deformation. In turn, this motif directs Tip's lysosomal trafficking and selective TCR downregulation. The amphipathic helix binds to the negatively charged lipids and induces liposome tubulation, the TM domain mediates oligomerization, and cooperation of the membrane-proximal helix with the TM domain is sufficient for localization to lipid rafts and lysosomal compartments, especially the mutivesicular bodies. These findings suggest that the membrane-proximal amphipathic helix and TM domain provide HVS Tip with the unique ability to deform the cellular membranes in lipid rafts and to downregulate TCRs potentially through MVB formation.

Original languageEnglish
Article numbere1000209
JournalPLoS pathogens
Volume4
Issue number11
DOIs
StatePublished - 1 Nov 2008

Cite this

Min, C. K., Bang, S. Y., Cho, B. A., Choi, Y. H., Yang, J. S., Lee, S. H., Seong, S. Y., Ki, W. K., Kim, S., Jae, U. J., Choi, M. S., Kim, I. S., & Cho, N. H. (2008). Role of amphipathic helix of a herpesviral protein in membrane deformation and T cell receptor downregulation. PLoS pathogens, 4(11), [e1000209]. https://doi.org/10.1371/journal.ppat.1000209