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| | ==NMR SOLUTION STRUCTURE OF THE HIV-1 VPU CYTOPLASMIC DOMAIN, 9 STRUCTURES== | | ==NMR SOLUTION STRUCTURE OF THE HIV-1 VPU CYTOPLASMIC DOMAIN, 9 STRUCTURES== |
| - | <StructureSection load='1vpu' size='340' side='right'caption='[[1vpu]], [[NMR_Ensembles_of_Models | 9 NMR models]]' scene=''> | + | <StructureSection load='1vpu' size='340' side='right'caption='[[1vpu]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1vpu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VPU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1vpu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VPU FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SYNTHETIC GENE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=1vpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vpu OCA], [https://pdbe.org/1vpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vpu RCSB], [https://www.ebi.ac.uk/pdbsum/1vpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vpu 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=1vpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vpu OCA], [https://pdbe.org/1vpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vpu RCSB], [https://www.ebi.ac.uk/pdbsum/1vpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vpu 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: Human immunodeficiency virus 1]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hoffmann, S]] | + | [[Category: Hoffmann S]] |
| - | [[Category: Rosch, P]] | + | [[Category: Rosch P]] |
| - | [[Category: Willbold, D]] | + | [[Category: Willbold D]] |
| - | [[Category: Aid]]
| + | |
| - | [[Category: Hiv]]
| + | |
| - | [[Category: Vpu]]
| + | |
| 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 human immunodeficiency virus type 1 Vpu protein enhances virus particle release from infected cells, decreases the tendency of syncytia formation and induces degradation of human CD4 receptor. It is known that the cytoplasmic part of Vpu is responsible for direct interaction to and degradation of CD4. The tertiary fold of the Vpu cytoplasmic domain in aqueous solution was determined employing NMR spectroscopy and molecular-dynamics simulated-annealing protocols. We found a very well defined amphipathic alpha-helix in the membrane proximal part (40-50), a less well defined helix (60-68), and a short alpha-helix at the C-terminus (75-79). We further determined the overall tertiary structure based on long-range nuclear Overhauser enhancement effects. Correlation of results from mutation experiments of Vpu and the structure data is discussed.
Secondary structure and tertiary fold of the human immunodeficiency virus protein U (Vpu) cytoplasmic domain in solution.,Willbold D, Hoffmann S, Rosch P Eur J Biochem. 1997 May 1;245(3):581-8. PMID:9182993[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Willbold D, Hoffmann S, Rosch P. Secondary structure and tertiary fold of the human immunodeficiency virus protein U (Vpu) cytoplasmic domain in solution. Eur J Biochem. 1997 May 1;245(3):581-8. PMID:9182993
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