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1vpc

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Revision as of 00:53, 12 September 2015

C-TERMINAL DOMAIN (52-96) OF THE HIV-1 REGULATORY PROTEIN VPR, NMR, 1 STRUCTURE

Structural highlights

1vpc is a 1 chain structure with sequence from 9hiv1. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[VPR_HV1B9] Involved in the transport of the viral pre-integration (PIC) complex to the nucleus during the early stages of the infection. This function is crucial for viral infection of non-dividing macrophages. May interact with karyopherin alpha/KPNA1 and KPNA2 to increase their affinity for proteins containing basic-type nuclear localization signal, including the viral matrix protein MA, thus facilitating the translocation of the viral genome into the nucleus. May also act directly at the nuclear pore complex, by binding nucleoporins phenylalanine-glycine (FG)-repeat regions (By similarity). May target specific host proteins for degradation by the 26S proteasome. Acts by associating with the cellular CUL4A-DDB1 E3 ligase complex through direct interaction with host VPRPB/DCAF-1. This change in the E3 ligase substrate specificity would result in cell cycle arrest or apoptosis in infected cells. Prevents infected cells from undergoing mitosis and proliferating, by inducing arrest or delay in the G2 phase of the cell cycle. This arrest creates a favorable environment for maximizing viral expression and production by rendering the HIV-1 LTR transcriptionally more active. In this context, Vpr stimulates gene expression driven by the HIV-1 LTR by interacting with human SP1, TFIIB and TFIID. Cell cycle arrest reportedly occurs within hours of infection and is not blocked by antiviral agents, suggesting that it is initiated by the Vpr carried into the virion. Additionally, Vpr induces apoptosis in a cell cycle dependent manner suggesting that these two effects are mechanistically linked. Interacts with mitochondrial permeability transition pore complex (PTPC). This interaction induces a rapid dissipation of the mitochondrial transmembrane potential, and mitochondrial release of apoptogenic proteins such as cytochrome C or apoptosis inducing factors. Detected in the serum and cerebrospinal fluid of AIDS patient, Vpr may also induce cell death to bystander cells (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 regulatory protein Vpr (96 amino acid residues) is incorporated into the virus particle through a mechanism involving its interaction with the C-terminal portion of Gag. Vpr potentiates virus replication by interrupting cell division in the G2 phase and participates in the nuclear transport of proviral DNA. The domain encompassing the 40 C-terminal residues of Vpr was shown to be involved in cell cycle arrest and binding of nucleocapsid protein NCp7, and suggested to promote nuclear provirus transfer. Accordingly, we show here that the synthetic 52-96 but not 1-51 sequences of Vpr interact with HIV-1 RNA. Based on these results, the structure of (52-96)Vpr was analysed by two-dimensional 1H-NMR in aqueous TFE (30%) solution and refined by restrained molecular dynamics. The structure is characterized by a long (53-78) amphipathic alpha-helix, followed by a less defined (79-96) C-terminal domain. The Leu60 and Leu67 side-chains are located on the hydrophobic side of the helix, suggesting their involvement in Vpr dimerization through a leucine zipper-type mechanism. Accordingly, their replacement by Ala eliminates Vpr dimerization in the two hybrid systems, while mutations of Ile74 and Ile81 have no effect. This was confirmed by gel filtration measurements and circular dichroism, which also showed that the alpha-helix still exists in (52-96)Vpr and its Ala60, Ala67 mutant in the presence and absence of TFE. Based on these results, a model of the coiled-coil Vpr dimer has been described, and its biological relevance as well as that of the structural characteristics of the 52-96 domain for the different functions of Vpr, including HIV-1 RNA binding, are discussed.

NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein Vpr: molecular insights into its biological functions.,Schuler W, Wecker K, de Rocquigny H, Baudat Y, Sire J, Roques BP J Mol Biol. 1999 Feb 5;285(5):2105-17. PMID:9925788^[1]

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

References

↑ Schuler W, Wecker K, de Rocquigny H, Baudat Y, Sire J, Roques BP. NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein Vpr: molecular insights into its biological functions. J Mol Biol. 1999 Feb 5;285(5):2105-17. PMID:9925788 doi:10.1006/jmbi.1998.2381

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1vpc"

@@ Line 2: / Line 2: @@
 <StructureSection load='1vpc' size='340' side='right' caption='[[1vpc]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1vpc]] is a 1 chain structure with sequence from [http://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=1VPC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VPC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1vpc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VPC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VPC FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vpc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1vpc RCSB], [http://www.ebi.ac.uk/pdbsum/1vpc PDBsum]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vpc OCA], [http://pdbe.org/1vpc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vpc RCSB], [http://www.ebi.ac.uk/pdbsum/1vpc PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 25: / Line 25: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1vpc" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human immunodeficiency virus 1]]
 [[Category: Baudat, Y]]
 [[Category: Rocquigny, H De]]

1vpc

From Proteopedia

Revision as of 00:53, 12 September 2015

C-TERMINAL DOMAIN (52-96) OF THE HIV-1 REGULATORY PROTEIN VPR, NMR, 1 STRUCTURE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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