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

PLoS Pathogens

Jae Ung Jung¹  Jae-Seong Yang¹  Chan-Ki Min²  Sun-Young Bang²  Yun-Hui Choi²  Seung-Yong Seong²  Nam-Hyuk Cho²  Bon-A Cho²  Ik-Sang Kim²  Myung-Sik Choi³  Sanguk Kim⁴  Ki Woo Kim⁵  Sun-Hwa Lee⁵ 

[1] Department of Life Science and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea;Department of Microbiology and Immunology, College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Korea;Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, Los Angeles, California, United States of America;National Instrumentation Center for Environmental Management, Seoul National University, Gwanak-Gu, Seoul, Korea;Seoul National University Hospital, Innovative Research Institute for Cell Therapy, Chongno-Gu, Seoul, Korea

关键词: Lipids;    T cells;    Liposomes;    Membrane trafficking;    Cell membranes;    Lysosomes;    Membrane proteins;    Integral membrane proteins;   

DOI  :  10.1371/journal.ppat.1000209

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY