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| | ==Solution fold of HIV-1 Virus protein U cytoplasmic domain in the presence of DPC micelles== | | ==Solution fold of HIV-1 Virus protein U cytoplasmic domain in the presence of DPC micelles== |
| - | <StructureSection load='2k7y' size='340' side='right'caption='[[2k7y]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2k7y' size='340' side='right'caption='[[2k7y]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k7y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hiv-1 Hiv-1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K7Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K7Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k7y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(SF162_ISOLATE) Human immunodeficiency virus type 1 (SF162 ISOLATE)]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K7Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K7Y FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vpu ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11691 HIV-1])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k7y OCA], [https://pdbe.org/2k7y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k7y RCSB], [https://www.ebi.ac.uk/pdbsum/2k7y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k7y ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k7y OCA], [https://pdbe.org/2k7y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k7y RCSB], [https://www.ebi.ac.uk/pdbsum/2k7y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k7y ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/VPU_HV1S1 VPU_HV1S1]] 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 interfere with 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 (By similarity).
| + | [https://www.uniprot.org/uniprot/VPU_HV1S1 VPU_HV1S1] 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 interfere with 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 (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hiv-1]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Koenig, B W]] | + | [[Category: Koenig BW]] |
| - | [[Category: Willbold, D]] | + | [[Category: Willbold D]] |
| - | [[Category: Wittlich, M]] | + | [[Category: Wittlich M]] |
| - | [[Category: Aid]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Host-virus interaction]]
| + | |
| - | [[Category: Ion transport]]
| + | |
| - | [[Category: Ionic channel]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Transport]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
VPU_HV1S1 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 interfere with 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 (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The HIV-1 encoded virus protein U (VpU) is required for efficient viral release from human host cells and for induction of CD4 degradation in the endoplasmic reticulum. The cytoplasmic domain of the membrane protein VpU (VpUcyt) is essential for the latter activity. The structure and dynamics of VpUcyt were characterized in the presence of membrane simulating dodecylphosphatidylcholine (DPC) micelles by high-resolution liquid state NMR. VpUcyt is unstructured in aqueous buffer. The addition of DPC micelles induces a well-defined membrane proximal alpha-helix (residues I39-E48) and an additional helical segment (residues L64-R70). A tight loop (L73-V78) is observed close to the C-terminus, whereas the interhelical linker (R49-E63) remains highly flexible. A 3D structure of VpUcyt in the presence of DPC micelles was calculated from a large set of proton-proton distance constraints. The topology of micelle-associated VpUcyt was derived from paramagnetic relaxation enhancement of protein nuclear spins after the introduction of paramagnetic probes into the interior of the micelle or the aqueous buffer. Qualitative analysis of secondary chemical shift and paramagnetic relaxation enhancement data in conjunction with dynamic information from heteronuclear NOEs and structural insight from homonuclear NOE-based distance constraints indicated that micelle-associated VpUcyt retains a substantial degree of structural flexibility.
NMR structural characterization of HIV-1 virus protein U cytoplasmic domain in the presence of dodecylphosphatidylcholine micelles.,Wittlich M, Koenig BW, Stoldt M, Schmidt H, Willbold D FEBS J. 2009 Nov;276(22):6560-75. Epub 2009 Oct 5. PMID:19804408[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wittlich M, Koenig BW, Stoldt M, Schmidt H, Willbold D. NMR structural characterization of HIV-1 virus protein U cytoplasmic domain in the presence of dodecylphosphatidylcholine micelles. FEBS J. 2009 Nov;276(22):6560-75. Epub 2009 Oct 5. PMID:19804408 doi:10.1111/j.1742-4658.2009.07363.x
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