Role of amphipathic helix of a herpesviral protein in membrane deformation and T cell receptor downregulation.
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.
Min
Chan-Ki
CK
Department of Microbiology and Immunology, College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Korea.
Bang
Sun-Young
SY
Cho
Bon-A
BA
Choi
Yun-Hui
YH
Yang
Jae-Seong
JS
Lee
Sun-Hwa
SH
Seong
Seung-Yong
SY
Kim
Ki Woo
KW
Kim
Sanguk
S
Jung
Jae Ung
JU
Choi
Myung-Sik
MS
Kim
Ik-Sang
IS
Cho
Nam-Hyuk
NH
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*
D015704:CD4 Antigens; D008055:Lipids; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2