%0 Journal Article %1 skasko_hiv-1_2012 %A Skasko, Mark %A Wang, Yan %A Tian, Ye %A Tokarev, Andrey %A Munguia, Jason %A Ruiz, Autumn %A Stephens, Edward B %A Opella, Stanley J %A Guatelli, John %D 2012 %J J. Biol. Chem. %K Accessory Acid Amino Binding,Protein Cells,Human Data,Nuclear Hydrophilic Immunodeficiency Interactions,Immunity,Innate,Lipid Magnetic Membrane,GPI-Linked Proteins Proteins,HIV-1,HeLa Proteins,Humans,Hydrophobic Regulatory Resonance,Protein Sequence Sequence,Antigens,Biomolecular,CD,Cell Structure,Secondary,Tertiary,Thermodynamics,Viral Virus and bilayers,Micelles,Models,Molecular,Molecular %N 1 %P 58--67 %R 10.1074/jbc.M111.296772 %T \HIV\-1 \Vpu\ protein antagonizes innate restriction factor \BST\-2 via lipid-embedded helix-helix interactions %V 287 %X The Vpu protein of HIV-1 antagonizes BST-2 (tetherin), a broad spectrum effector of the innate immune response to viral infection, by an intermolecular interaction that maps genetically to the $\alpha$-helical transmembrane domains (TMDs) of each protein. Here we utilize NMR spectroscopy to describe key features of the helix-helix pairing that underlies this interaction. The antagonism of BST-2 involves a sequence of three alanines and a tryptophan spaced at four residue intervals within the Vpu TMD helix. Responsiveness to Vpu involves bulky hydrophobic residues in the C-terminal region of the BST-2 TMD helix that likely fit between the alanines on the interactive face of Vpu. These aspects of Vpu and BST-2 form an anti-parallel, lipid-embedded helix-helix interface. Changes in human BST-2 that mimic sequences found in nonhuman primate orthologs unresponsive to Vpu change the tilt angle of the TMD in the lipid bilayer without abrogating its intrinsic ability to interact with Vpu. These data explain the mechanism by which HIV-1 evades a key aspect of innate immunity and the species specificity of Vpu using an anti-parallel helix-helix packing model.

@article{skasko_hiv-1_2012, abstract = {The Vpu protein of HIV-1 antagonizes BST-2 (tetherin), a broad spectrum effector of the innate immune response to viral infection, by an intermolecular interaction that maps genetically to the $\alpha$-helical transmembrane domains (TMDs) of each protein. Here we utilize NMR spectroscopy to describe key features of the helix-helix pairing that underlies this interaction. The antagonism of BST-2 involves a sequence of three alanines and a tryptophan spaced at four residue intervals within the Vpu TMD helix. Responsiveness to Vpu involves bulky hydrophobic residues in the C-terminal region of the BST-2 TMD helix that likely fit between the alanines on the interactive face of Vpu. These aspects of Vpu and BST-2 form an anti-parallel, lipid-embedded helix-helix interface. Changes in human BST-2 that mimic sequences found in nonhuman primate orthologs unresponsive to Vpu change the tilt angle of the TMD in the lipid bilayer without abrogating its intrinsic ability to interact with Vpu. These data explain the mechanism by which HIV-1 evades a key aspect of innate immunity and the species specificity of Vpu using an anti-parallel helix-helix packing model.}, added-at = {2017-03-14T02:48:56.000+0100}, author = {Skasko, Mark and Wang, Yan and Tian, Ye and Tokarev, Andrey and Munguia, Jason and Ruiz, Autumn and Stephens, Edward B and Opella, Stanley J and Guatelli, John}, biburl = {https://www.bibsonomy.org/bibtex/2a7d19ed6c984cd29caff0cc33901997c/nmrresource}, doi = {10.1074/jbc.M111.296772}, interhash = {0dc7dbd6d831ac72ef032a4118922883}, intrahash = {a7d19ed6c984cd29caff0cc33901997c}, issn = {1083-351X}, journal = {J. Biol. Chem.}, keywords = {Accessory Acid Amino Binding,Protein Cells,Human Data,Nuclear Hydrophilic Immunodeficiency Interactions,Immunity,Innate,Lipid Magnetic Membrane,GPI-Linked Proteins Proteins,HIV-1,HeLa Proteins,Humans,Hydrophobic Regulatory Resonance,Protein Sequence Sequence,Antigens,Biomolecular,CD,Cell Structure,Secondary,Tertiary,Thermodynamics,Viral Virus and bilayers,Micelles,Models,Molecular,Molecular}, month = jan, number = 1, pages = {58--67}, pmid = {22072710}, timestamp = {2017-03-14T02:49:21.000+0100}, title = {{{\{}HIV{\}}-1 {\{}Vpu{\}} protein antagonizes innate restriction factor {\{}BST{\}}-2 via lipid-embedded helix-helix interactions}}, volume = 287, year = 2012 }