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{{STRUCTURE_4cc9|  PDB=4cc9  |  SCENE=  }}
===Crystal structure of human SAMHD1 (amino acid residues 582-626) bound to Vpx isolated from sooty mangabey and human DCAF1 (amino acid residues 1058-1396)===


==Disease==
==Crystal structure of human SAMHD1 (amino acid residues 582-626) bound to Vpx isolated from sooty mangabey and human DCAF1 (amino acid residues 1058-1396)==
[[http://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Defects in SAMHD1 are the cause of Aicardi-Goutieres syndrome type 5 (AGS5) [MIM:[http://omim.org/entry/612952 612952]]. A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.<ref>PMID:19525956</ref> <ref>PMID:20842748</ref>  Defects in SAMHD1 are the cause of chilblain lupus type 2 (CHBL2) [MIM:[http://omim.org/entry/614415 614415]]. A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure at temperatures less than 10 degrees centigrade.<ref>PMID:21204240</ref>
<StructureSection load='4cc9' size='340' side='right'caption='[[4cc9]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cc9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus Simian immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CC9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.473&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4cc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cc9 OCA], [https://pdbe.org/4cc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cc9 RCSB], [https://www.ebi.ac.uk/pdbsum/4cc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cc9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DCAF1_HUMAN DCAF1_HUMAN] Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination. Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:23362280). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription. H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714).<ref>PMID:16964240</ref> <ref>PMID:17609381</ref> <ref>PMID:17630831</ref> <ref>PMID:18332868</ref> <ref>PMID:18524771</ref> <ref>PMID:18606781</ref> <ref>PMID:19287380</ref> <ref>PMID:20644714</ref> <ref>PMID:22184063</ref> <ref>PMID:23063525</ref> <ref>PMID:23362280</ref> <ref>PMID:24140421</ref>  (Microbial infection) In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT.<ref>PMID:17314515</ref> <ref>PMID:17559673</ref> <ref>PMID:17609381</ref> <ref>PMID:17620334</ref> <ref>PMID:17626091</ref> <ref>PMID:17630831</ref> <ref>PMID:18524771</ref> <ref>PMID:24116224</ref>  (Microbial infection) In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage.<ref>PMID:17314515</ref> <ref>PMID:18464893</ref> <ref>PMID:19264781</ref> <ref>PMID:19923175</ref> <ref>PMID:24336198</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection of myeloid-lineage cells as well as resting CD4+ T cells by reducing the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function. In other lentiviruses, including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation. The molecular mechanism by which these viral proteins are able to usurp the host cell's ubiquitination machinery to destroy the cell's protection against these viruses has not been defined. Here we present the crystal structure of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical bundle stabilized by a zinc finger motif, and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure reported here provides a molecular description of how a lentiviral accessory protein is able to subvert the cell's normal protein degradation pathway to inactivate the cellular viral defence system.


==Function==
Structural basis of lentiviral subversion of a cellular protein degradation pathway.,Schwefel D, Groom HC, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IA Nature. 2013 Dec 15. doi: 10.1038/nature12815. PMID:24336198<ref>PMID:24336198</ref>
[[http://www.uniprot.org/uniprot/VPRBP_HUMAN VPRBP_HUMAN]] Component of the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex, VprBP/DCAF1 may function as the substrate recognition module within this complex. For example, VprBP/DCAF1 targets NF2 to the E3 ubiquitin-ligase complex for ubiquitination and subsequent proteasome-dependent degradation. In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1 function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1 function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage. Associated with chromatin in a DDB1-independent and cell cycle-dependent manner, VprBP/DCAF1 is recruited to chromatin as DNA is being replicated and is released from chromatin before mitosis.<ref>PMID:17314515</ref> <ref>PMID:17620334</ref> <ref>PMID:17626091</ref> <ref>PMID:17630831</ref> <ref>PMID:17609381</ref> <ref>PMID:17559673</ref> <ref>PMID:18524771</ref> <ref>PMID:18606781</ref> <ref>PMID:18332868</ref> <ref>PMID:18464893</ref> <ref>PMID:19264781</ref> <ref>PMID:19923175</ref> <ref>PMID:23063525</ref>  [[http://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Putative nuclease involved in innate immune response by acting as a negative regulator of the cell-intrinsic antiviral response. May play a role in mediating proinflammatory responses to TNF-alpha signaling.<ref>PMID:18546154</ref> <ref>PMID:19525956</ref> [[http://www.uniprot.org/uniprot/VPX_SIVSP VPX_SIVSP]] Plays a role in nuclear translocation of the viral pre-integration complex (PIC), thus is required for the virus to infect non-dividing cells. Targets 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 results in the degradation of host SAMHD1. In turn, SAMHD1 depletion allows viral replication in host myeloid cells by preventing SAMHD1-mediated hydrolysis of intracellular dNTPs necessary for reverse transcription.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4cc9]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CC9 OCA].
</div>
<div class="pdbe-citations 4cc9" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
<references group="xtra"/><references/>
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
[[Category: Bishop, K N.]]
*[[VprBP 3D structures|VprBP 3D structures]]
[[Category: Boucherit, V C.]]
== References ==
[[Category: Christodoulou, E.]]
<references/>
[[Category: Groom, H C.T.]]
__TOC__
[[Category: Schwefel, D.]]
</StructureSection>
[[Category: Stoye, J P.]]
[[Category: Homo sapiens]]
[[Category: Taylor, I A.]]
[[Category: Large Structures]]
[[Category: Walker, P A.]]
[[Category: Simian immunodeficiency virus]]
[[Category: Hiv]]
[[Category: Bishop KN]]
[[Category: Proteasomal degradation]]
[[Category: Boucherit VC]]
[[Category: Protein binding]]
[[Category: Christodoulou E]]
[[Category: Retroviral accessory protein]]
[[Category: Groom HCT]]
[[Category: Retroviral restriction factor]]
[[Category: Schwefel D]]
[[Category: Siv]]
[[Category: Stoye JP]]
[[Category: Ubiquitination]]
[[Category: Taylor IA]]
[[Category: Walker PA]]

Latest revision as of 14:11, 9 May 2024

Crystal structure of human SAMHD1 (amino acid residues 582-626) bound to Vpx isolated from sooty mangabey and human DCAF1 (amino acid residues 1058-1396)Crystal structure of human SAMHD1 (amino acid residues 582-626) bound to Vpx isolated from sooty mangabey and human DCAF1 (amino acid residues 1058-1396)

Structural highlights

4cc9 is a 3 chain structure with sequence from Homo sapiens and Simian immunodeficiency virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.473Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DCAF1_HUMAN Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination. Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:23362280). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription. H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] (Microbial infection) In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT.[13] [14] [15] [16] [17] [18] [19] [20] (Microbial infection) In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage.[21] [22] [23] [24] [25]

Publication Abstract from PubMed

Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection of myeloid-lineage cells as well as resting CD4+ T cells by reducing the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function. In other lentiviruses, including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation. The molecular mechanism by which these viral proteins are able to usurp the host cell's ubiquitination machinery to destroy the cell's protection against these viruses has not been defined. Here we present the crystal structure of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical bundle stabilized by a zinc finger motif, and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure reported here provides a molecular description of how a lentiviral accessory protein is able to subvert the cell's normal protein degradation pathway to inactivate the cellular viral defence system.

Structural basis of lentiviral subversion of a cellular protein degradation pathway.,Schwefel D, Groom HC, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IA Nature. 2013 Dec 15. doi: 10.1038/nature12815. PMID:24336198[26]

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

See Also

References

  1. ↑ Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature. 2006 Oct 5;443(7111):590-3. PMID:16964240 doi:10.1038/nature05175
  2. ↑ Hrecka K, Gierszewska M, Srivastava S, Kozaczkiewicz L, Swanson SK, Florens L, Washburn MP, Skowronski J. Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11778-83. Epub 2007 Jul 3. PMID:17609381 doi:http://dx.doi.org/10.1073/pnas.0702102104
  3. ↑ Belzile JP, Duisit G, Rougeau N, Mercier J, Finzi A, Cohen EA. HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase. PLoS Pathog. 2007 Jul;3(7):e85. PMID:17630831 doi:http://dx.doi.org/10.1371/journal.ppat.0030085
  4. ↑ Huang J, Chen J. VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene. 2008 Jul 3;27(29):4056-64. Epub 2008 Mar 10. PMID:18332868 doi:onc200844
  5. ↑ Le Rouzic E, Morel M, Ayinde D, Belaidouni N, Letienne J, Transy C, Margottin-Goguet F. Assembly with the Cul4A-DDB1DCAF1 ubiquitin ligase protects HIV-1 Vpr from proteasomal degradation. J Biol Chem. 2008 Aug 1;283(31):21686-92. doi: 10.1074/jbc.M710298200. Epub 2008 , Jun 4. PMID:18524771 doi:http://dx.doi.org/10.1074/jbc.M710298200
  6. ↑ McCall CM, Miliani de Marval PL, Chastain PD 2nd, Jackson SC, He YJ, Kotake Y, Cook JG, Xiong Y. Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol. 2008 Sep;28(18):5621-33. doi: 10.1128/MCB.00232-08. Epub 2008 Jul , 7. PMID:18606781 doi:http://dx.doi.org/10.1128/MCB.00232-08
  7. ↑ Maddika S, Chen J. Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase. Nat Cell Biol. 2009 Apr;11(4):409-19. doi: 10.1038/ncb1848. Epub 2009 Mar 15. PMID:19287380 doi:10.1038/ncb1848
  8. ↑ Tamori Y, Bialucha CU, Tian AG, Kajita M, Huang YC, Norman M, Harrison N, Poulton J, Ivanovitch K, Disch L, Liu T, Deng WM, Fujita Y. Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol. 2010 Jul 13;8(7):e1000422. doi: 10.1371/journal.pbio.1000422. PMID:20644714 doi:http://dx.doi.org/10.1371/journal.pbio.1000422
  9. ↑ Kim K, Heo K, Choi J, Jackson S, Kim H, Xiong Y, An W. Vpr-binding protein antagonizes p53-mediated transcription via direct interaction with H3 tail. Mol Cell Biol. 2012 Feb;32(4):783-96. doi: 10.1128/MCB.06037-11. Epub 2011 Dec, 19. PMID:22184063 doi:http://dx.doi.org/10.1128/MCB.06037-11
  10. ↑ Lee JM, Lee JS, Kim H, Kim K, Park H, Kim JY, Lee SH, Kim IS, Kim J, Lee M, Chung CH, Seo SB, Yoon JB, Ko E, Noh DY, Kim KI, Kim KK, Baek SH. EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Mol Cell. 2012 Nov 30;48(4):572-86. doi: 10.1016/j.molcel.2012.09.004. Epub 2012 , Oct 11. PMID:23063525 doi:http://dx.doi.org/10.1016/j.molcel.2012.09.004
  11. ↑ Jung HY, Wang X, Jun S, Park JI. Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation. J Biol Chem. 2013 Mar 8;288(10):7252-62. doi: 10.1074/jbc.M112.416792. Epub 2013 , Jan 28. PMID:23362280 doi:http://dx.doi.org/10.1074/jbc.M112.416792
  12. ↑ Kim K, Kim JM, Kim JS, Choi J, Lee YS, Neamati N, Song JS, Heo K, An W. VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription. Mol Cell. 2013 Nov 7;52(3):459-67. doi: 10.1016/j.molcel.2013.09.017. Epub 2013, Oct 17. PMID:24140421 doi:http://dx.doi.org/10.1016/j.molcel.2013.09.017
  13. ↑ Le Rouzic E, Belaidouni N, Estrabaud E, Morel M, Rain JC, Transy C, Margottin-Goguet F. HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. Cell Cycle. 2007 Jan 15;6(2):182-8. Epub 2007 Jan 17. PMID:17314515
  14. ↑ DeHart JL, Zimmerman ES, Ardon O, Monteiro-Filho CM, Arganaraz ER, Planelles V. HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Virol J. 2007 Jun 8;4:57. PMID:17559673 doi:http://dx.doi.org/10.1186/1743-422X-4-57
  15. ↑ Hrecka K, Gierszewska M, Srivastava S, Kozaczkiewicz L, Swanson SK, Florens L, Washburn MP, Skowronski J. Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11778-83. Epub 2007 Jul 3. PMID:17609381 doi:http://dx.doi.org/10.1073/pnas.0702102104
  16. ↑ Wen X, Duus KM, Friedrich TD, de Noronha CM. The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor. J Biol Chem. 2007 Sep 14;282(37):27046-57. Epub 2007 Jul 9. PMID:17620334 doi:http://dx.doi.org/10.1074/jbc.M703955200
  17. ↑ Tan L, Ehrlich E, Yu XF. DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. J Virol. 2007 Oct;81(19):10822-30. Epub 2007 Jul 11. PMID:17626091 doi:http://dx.doi.org/10.1128/JVI.01380-07
  18. ↑ Belzile JP, Duisit G, Rougeau N, Mercier J, Finzi A, Cohen EA. HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase. PLoS Pathog. 2007 Jul;3(7):e85. PMID:17630831 doi:http://dx.doi.org/10.1371/journal.ppat.0030085
  19. ↑ Le Rouzic E, Morel M, Ayinde D, Belaidouni N, Letienne J, Transy C, Margottin-Goguet F. Assembly with the Cul4A-DDB1DCAF1 ubiquitin ligase protects HIV-1 Vpr from proteasomal degradation. J Biol Chem. 2008 Aug 1;283(31):21686-92. doi: 10.1074/jbc.M710298200. Epub 2008 , Jun 4. PMID:18524771 doi:http://dx.doi.org/10.1074/jbc.M710298200
  20. ↑ Maudet C, Sourisce A, Dragin L, Lahouassa H, Rain JC, Bouaziz S, Ramirez BC, Margottin-Goguet F. HIV-1 Vpr induces the degradation of ZIP and sZIP, adaptors of the NuRD chromatin remodeling complex, by hijacking DCAF1/VprBP. PLoS One. 2013 Oct 8;8(10):e77320. doi: 10.1371/journal.pone.0077320. eCollection, 2013. PMID:24116224 doi:http://dx.doi.org/10.1371/journal.pone.0077320
  21. ↑ Le Rouzic E, Belaidouni N, Estrabaud E, Morel M, Rain JC, Transy C, Margottin-Goguet F. HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. Cell Cycle. 2007 Jan 15;6(2):182-8. Epub 2007 Jan 17. PMID:17314515
  22. ↑ Srivastava S, Swanson SK, Manel N, Florens L, Washburn MP, Skowronski J. Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS Pathog. 2008 May 9;4(5):e1000059. doi: 10.1371/journal.ppat.1000059. PMID:18464893 doi:http://dx.doi.org/10.1371/journal.ppat.1000059
  23. ↑ Bergamaschi A, Ayinde D, David A, Le Rouzic E, Morel M, Collin G, Descamps D, Damond F, Brun-Vezinet F, Nisole S, Margottin-Goguet F, Pancino G, Transy C. The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection. J Virol. 2009 May;83(10):4854-60. doi: 10.1128/JVI.00187-09. Epub 2009 Mar 4. PMID:19264781 doi:http://dx.doi.org/10.1128/JVI.00187-09
  24. ↑ Gramberg T, Sunseri N, Landau NR. Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx. J Virol. 2010 Feb;84(3):1387-96. doi: 10.1128/JVI.01437-09. Epub 2009 Nov 18. PMID:19923175 doi:http://dx.doi.org/10.1128/JVI.01437-09
  25. ↑ Schwefel D, Groom HC, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IA. Structural basis of lentiviral subversion of a cellular protein degradation pathway. Nature. 2013 Dec 15. doi: 10.1038/nature12815. PMID:24336198 doi:http://dx.doi.org/10.1038/nature12815
  26. ↑ Schwefel D, Groom HC, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IA. Structural basis of lentiviral subversion of a cellular protein degradation pathway. Nature. 2013 Dec 15. doi: 10.1038/nature12815. PMID:24336198 doi:http://dx.doi.org/10.1038/nature12815

4cc9, resolution 2.47Å

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