2n28 | pdb_00002n28
Solid-state NMR structure of Vpu
Structural highlights
Function[VPU_HV1H3] Enhances virion budding, by targeting human CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its receptor human CD4 in the endoplasmic reticulum. Degradation of antiretroviral protein Tetherin/BST2 is important for virion budding, as BST2 tethers new viral particles to the host cell membrane. Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, a substrate recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin ligase, induces their ubiquitination and subsequent proteasomal degradation. The alteration of the E3 ligase specificity by Vpu seems to promote the degradation of host IKBKB, leading to NF-kappa-B down-regulation and subsequent apoptosis. Ion channel activity has also been suggested, however, formation of cation-selective channel has been reconstituted ex-vivo in lipid bilayers. It is thus unsure that this activity plays a role in vivo.[UniProtKB:P05919] Publication Abstract from PubMedVirus protein U (Vpu) from HIV-1, a small membrane protein composed of a transmembrane helical domain and two alpha-helices in an amphipathic cytoplasmic domain, down modulates several cellular proteins, including CD4, BST-2/CD317/tetherin, NTB-A, and CCR7. The interactions of Vpu with these proteins interfere with the immune system and enhance the release of newly synthesized virus particles. It is essential to characterize the structure and dynamics of Vpu in order to understand the mechanisms of the protein-protein interactions, and potentially to discover antiviral drugs. In this article, we describe investigations of the cytoplasmic domain of Vpu as well as full-length Vpu by NMR spectroscopy. These studies are complementary to earlier analysis of the transmembrane domain of Vpu. The results suggest that the two helices in the cytoplasmic domain form a U-shape. The length of the inter-helical loop in the cytoplasmic domain and the orientation of the third helix vary with the lipid composition, which demonstrate that the C-terminal helix is relatively flexible, providing accessibility for interaction partners. Structural determination of virus protein U from HIV-1 by NMR in membrane environments.,Zhang H, Lin EC, Das BB, Tian Y, Opella SJ Biochim Biophys Acta. 2015 Sep 8. pii: S0005-2736(15)00293-X. doi:, 10.1016/j.bbamem.2015.09.008. PMID:26362058[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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