title: Role of amphipathic helix of a herpesviral protein in membrane deformation and T cell receptor downregulation.
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.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Korea.
authors.forename: Chan-Ki
authors.initials: CK
authors.lastname: Min
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Bang
authors.forename: Bon-A
authors.initials: BA
authors.lastname: Cho
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Choi
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Yang
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seong
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: Jae Ung
authors.initials: JU
authors.lastname: Jung
authors.forename: Myung-Sik
authors.initials: MS
authors.lastname: Choi
authors.forename: Ik-Sang
authors.initials: IS
authors.lastname: Kim
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
mesh_terms: D015704:CD4 Antigens; D002462:Cell Membrane / Q000648:ultrastructure / Q000821:virology*; D015536:Down-Regulation; D006567:Herpesvirus 2, Saimiriine / Q000201:enzymology*; D006801:Humans; D019169:Jurkat Cells; D008055:Lipids; D008247:Lysosomes; D021962:Membrane Microdomains / Q000378:metabolism / Q000821:virology; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000648:ultrastructure / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D008055:Lipids; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2