2n29

From Proteopedia

(Difference between revisions)

Revision as of 08:14, 8 March 2023

Solution-state NMR structure of Vpu cytoplasmic domain

Structural highlights

2n29 is a 1 chain structure with sequence from Human immunodeficiency virus 1. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VPU_HV1H2 Enhances virion budding by targeting host CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its host receptor 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.[HAMAP-Rule:MF_04082]^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Virus 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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Akari H, Bour S, Kao S, Adachi A, Strebel K. The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappaB-dependent expression of antiapoptotic factors. J Exp Med. 2001 Nov 5;194(9):1299-311. PMID:11696595 doi:10.1084/jem.194.9.1299
↑ Mangeat B, Gers-Huber G, Lehmann M, Zufferey M, Luban J, Piguet V. HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog. 2009 Sep;5(9):e1000574. PMID:19730691 doi:10.1371/journal.ppat.1000574
↑ Iwabu Y, Fujita H, Kinomoto M, Kaneko K, Ishizaka Y, Tanaka Y, Sata T, Tokunaga K. HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. J Biol Chem. 2009 Dec 11;284(50):35060-72. PMID:19837671 doi:10.1074/jbc.M109.058305
↑ Pham TN, Lukhele S, Hajjar F, Routy JP, Cohen ÉA. HIV Nef and Vpu protect HIV-infected CD4+ T cells from antibody-mediated cell lysis through down-modulation of CD4 and BST2. Retrovirology. 2014 Feb 6;11:15. PMID:24498878 doi:10.1186/1742-4690-11-15
↑ Jia X, Weber E, Tokarev A, Lewinski M, Rizk M, Suarez M, Guatelli J, Xiong Y. Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1. Elife. 2014 Apr 29;3:e02362. doi: 10.7554/eLife.02362. PMID:24843023
↑ Ewart GD, Sutherland T, Gage PW, Cox GB. The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels. J Virol. 1996 Oct;70(10):7108-15. PMID:8794357 doi:10.1128/JVI.70.10.7108-7115.1996
↑ Zhang H, Lin EC, Das BB, Tian Y, Opella SJ. Structural determination of virus protein U from HIV-1 by NMR in membrane environments. Biochim Biophys Acta. 2015 Sep 8. pii: S0005-2736(15)00293-X. doi:, 10.1016/j.bbamem.2015.09.008. PMID:26362058 doi:http://dx.doi.org/10.1016/j.bbamem.2015.09.008

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2n29"

@@ Line 1: / Line 1: @@
 ==Solution-state NMR structure of Vpu cytoplasmic domain==
-<StructureSection load='2n29' size='340' side='right'caption='[[2n29]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
+<StructureSection load='2n29' size='340' side='right'caption='[[2n29]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2n29]] 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=2N29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N29 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2n29]] 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=2N29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N29 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2n28|2n28]]</div></td></tr>
+</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=2n29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n29 OCA], [https://pdbe.org/2n29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n29 RCSB], [https://www.ebi.ac.uk/pdbsum/2n29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n29 ProSAT]</span></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=11676 9HIV1])</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=2n29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n29 OCA], [https://pdbe.org/2n29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n29 RCSB], [https://www.ebi.ac.uk/pdbsum/2n29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n29 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/VPU_HV1H3 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]
+[https://www.uniprot.org/uniprot/VPU_HV1H2 VPU_HV1H2] Enhances virion budding by targeting host CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its host receptor 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.[HAMAP-Rule:MF_04082]<ref>PMID:11696595</ref> <ref>PMID:19730691</ref> <ref>PMID:19837671</ref> <ref>PMID:24498878</ref> <ref>PMID:24843023</ref> <ref>PMID:8794357</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human immunodeficiency virus 1]]
 [[Category: Large Structures]]
-[[Category: Das, B B]]
+[[Category: Das BB]]
-[[Category: Lin, E C]]
+[[Category: Lin EC]]
-[[Category: Opella, S J]]
+[[Category: Opella SJ]]
-[[Category: Tian, Y]]
+[[Category: Tian Y]]
-[[Category: Zhang, H]]
+[[Category: Zhang H]]
-[[Category: Alpha helix]]
-[[Category: Viral protein]]

2n29

From Proteopedia

Revision as of 08:14, 8 March 2023

Solution-state NMR structure of Vpu cytoplasmic domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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