%0 Journal Article %1 lewinski_membrane_2015 %A Lewinski, Mary K %A Jafari, Moein %A Zhang, Hua %A Opella, Stanley J %A Guatelli, John %D 2015 %J J. Biol. Chem. %K (HIV),Humans,Innate (NMR),Polymorphism,Proteolysis,Retrovirus,Tryptophan,Viral Accessory Antigens,CD,Cell Assembly Biology,Cell Cells,Human Immunity,Membrane Immunodeficiency Membrane,Cell Protein,GPI-Linked Proteins,Genetic,HIV-1,HeLa Proteins,Human Proteins,Virus Regulatory Surface Trafficking,Nuclear Virus and immunodeficiency magnetic resonance virus %N 17 %P 10919--10933 %R 10.1074/jbc.M114.630095 %T Membrane \Anchoring\ by a \C\-terminal \Tryptophan\ \Enables\ \HIV\-1 \Vpu\ to \Displace\ \Bone\ \Marrow\ \Stromal\ \Antigen\ 2 (\BST\2) from \Sites\ of \Viral\ \Assembly\ %V 290 %X The restriction factor BST2 (tetherin) prevents the release of enveloped viruses from the host cell and is counteracted by HIV-1 Vpu. Vpu and BST2 interact directly via their transmembrane domains. This interaction enables Vpu to induce the surface down-regulation and the degradation of BST2, but neither of these activities fully accounts for the ability of Vpu to enhance virion release. During a study of naturally occurring Vpu proteins, we found that a tryptophan residue near the Vpu C terminus is particularly important for enhancing virion release. Vpu proteins with a W76G polymorphism degraded and down-regulated BST2 from the cell surface, yet they inefficiently stimulated virion release. Here we explore the mechanism of this anomaly. We find that Trp-76 is critical for the ability of Vpu to displace BST2 from sites of viral assembly in the plane of the plasma membrane. This effect does not appear to involve a general reorganization of the membrane microdomains associated with virion assembly, but rather is a specific effect of Vpu on BST2. Using NMR spectroscopy, we find that the cytoplasmic domain of Vpu and Trp-76 specifically interact with lipids. Moreover, paramagnetic relaxation enhancement studies show that Trp-76 inserts into the lipid. These data are consistent with a model whereby Trp-76 anchors the C terminus of the cytoplasmic tail of Vpu to the plasma membrane, enabling the movement of Vpu-bound BST2 away from viral assembly sites.

@article{lewinski_membrane_2015, abstract = {The restriction factor BST2 (tetherin) prevents the release of enveloped viruses from the host cell and is counteracted by HIV-1 Vpu. Vpu and BST2 interact directly via their transmembrane domains. This interaction enables Vpu to induce the surface down-regulation and the degradation of BST2, but neither of these activities fully accounts for the ability of Vpu to enhance virion release. During a study of naturally occurring Vpu proteins, we found that a tryptophan residue near the Vpu C terminus is particularly important for enhancing virion release. Vpu proteins with a W76G polymorphism degraded and down-regulated BST2 from the cell surface, yet they inefficiently stimulated virion release. Here we explore the mechanism of this anomaly. We find that Trp-76 is critical for the ability of Vpu to displace BST2 from sites of viral assembly in the plane of the plasma membrane. This effect does not appear to involve a general reorganization of the membrane microdomains associated with virion assembly, but rather is a specific effect of Vpu on BST2. Using NMR spectroscopy, we find that the cytoplasmic domain of Vpu and Trp-76 specifically interact with lipids. Moreover, paramagnetic relaxation enhancement studies show that Trp-76 inserts into the lipid. These data are consistent with a model whereby Trp-76 anchors the C terminus of the cytoplasmic tail of Vpu to the plasma membrane, enabling the movement of Vpu-bound BST2 away from viral assembly sites.}, added-at = {2017-03-14T02:48:56.000+0100}, author = {Lewinski, Mary K and Jafari, Moein and Zhang, Hua and Opella, Stanley J and Guatelli, John}, biburl = {https://www.bibsonomy.org/bibtex/2cde50e4d5fa3c235f2df81d9e02e9d20/nmrresource}, doi = {10.1074/jbc.M114.630095}, interhash = {6b02b92af3914fc87fa096584919dc46}, intrahash = {cde50e4d5fa3c235f2df81d9e02e9d20}, issn = {1083-351X}, journal = {J. Biol. Chem.}, keywords = {(HIV),Humans,Innate (NMR),Polymorphism,Proteolysis,Retrovirus,Tryptophan,Viral Accessory Antigens,CD,Cell Assembly Biology,Cell Cells,Human Immunity,Membrane Immunodeficiency Membrane,Cell Protein,GPI-Linked Proteins,Genetic,HIV-1,HeLa Proteins,Human Proteins,Virus Regulatory Surface Trafficking,Nuclear Virus and immunodeficiency magnetic resonance virus}, month = apr, number = 17, pages = {10919--10933}, pmid = {25759385}, timestamp = {2017-03-14T02:49:21.000+0100}, title = {{Membrane {\{}Anchoring{\}} by a {\{}C{\}}-terminal {\{}Tryptophan{\}} {\{}Enables{\}} {\{}HIV{\}}-1 {\{}Vpu{\}} to {\{}Displace{\}} {\{}Bone{\}} {\{}Marrow{\}} {\{}Stromal{\}} {\{}Antigen{\}} 2 ({\{}BST{\}}2) from {\{}Sites{\}} of {\{}Viral{\}} {\{}Assembly{\}}}}, volume = 290, year = 2015 }