ArticleThe Journal of biological chemistry2013
HIV-2 and SIVmac accessory virulence factor Vpx down-regulates SAMHD1 enzyme catalysis prior to proteasome-dependent degradation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Development of Peptide Displacement Assays to Screen for Antagonists of DDB1 Interactions.Biochemistry · 2024Article
- SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks.Nature communications · 2022Article
- Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses.PLoS pathogens · 2021Article
- The role of SAMHD1 expression and its relation to HIV-2 (Vpx) gene production.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2018Review
- The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression.eLife · 2018Article
- SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity.Autoimmunity · 2018Review
- HIV-1 Vpr protein directly loads helicase-like transcription factor (HLTF) onto the CRL4-DCAF1 E3 ubiquitin ligase.The Journal of biological chemistry · 2017Article
- Inhibition of Vpx-Mediated SAMHD1 and Vpr-Mediated Host Helicase Transcription Factor Degradation by Selective Disruption of Viral CRL4 (DCAF1) E3 Ubiquitin Ligase Assembly.Journal of virology · 2017Article
- Substrate Specificity of SAMHD1 Triphosphohydrolase Activity Is Controlled by Deoxyribonucleoside Triphosphates and Phosphorylation at Thr592.Biochemistry · 2016Article
- The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction.Nature structural & molecular biology · 2016Article
- SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr).The Journal of biological chemistry · 2016Article
- The Deoxynucleoside Triphosphate Triphosphohydrolase Activity of SAMHD1 Protein Contributes to the Mitochondrial DNA Depletion Associated with Genetic Deficiency of Deoxyguanosine Kinase.The Journal of biological chemistry · 2015Article
- Structural Basis of Clade-specific Engagement of SAMHD1 (Sterile α Motif and Histidine/Aspartate-containing Protein 1) Restriction Factors by Lentiviral Viral Protein X (Vpx) Virulence Factors.The Journal of biological chemistry · 2015Article
- Degradation of SAMHD1 by Vpx Is Independent of Uncoating.Journal of virology · 2015Article
- Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr.Virology · 2015Article
- Cyclin L2 is a critical HIV dependency factor in macrophages that controls SAMHD1 abundance.Cell host & microbe · 2015Article
- Structural basis of allosteric activation of sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) by nucleoside triphosphates.The Journal of biological chemistry · 2014Article
- Vpx rescue of HIV-1 from the antiviral state in mature dendritic cells is independent of the intracellular deoxynucleotide concentration.Retrovirology · 2014Article
- Mechanisms of allosteric activation and inhibition of the deoxyribonucleoside triphosphate triphosphohydrolase from Enterococcus faecalis.The Journal of biological chemistry · 2014Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
SAMHD1, a dGTP-regulated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase, down-regulates dNTP pools in terminally differentiated and quiescent cells, thereby inhibiting HIV-1 infection at the reverse transcription step. HIV-2 and simian immunodeficiency virus (SIV) counteract this restriction via a virion-associated virulence accessory factor, Vpx (Vpr in some SIVs), which loads SAMHD1 onto CRL4-DCAF1 E3 ubiquitin ligase for polyubiquitination, programming it for proteasome-dependent degradation. However, the detailed molecular mechanisms of SAMHD1 recruitment to the E3 ligase have not been defined. Further, whether divergent, orthologous Vpx proteins, encoded by distinct HIV/SIV strains, bind SAMHD1 in a similar manner, at a molecular level, is not known. We applied surface plasmon resonance analysis to assess the requirements for and kinetics of binding between various primate SAMHD1 proteins and Vpx proteins from SIV or HIV-2 strains. Our data indicate that Vpx proteins, bound to DCAF1, interface with the C terminus of primate SAMHD1 proteins with nanomolar affinity, manifested by rapid association and slow dissociation. Further, we provide evidence that Vpx binding to SAMHD1 inhibits its catalytic activity and induces disassembly of a dGTP-dependent oligomer. Our studies reveal a previously unrecognized biochemical mechanism of Vpx-mediated SAMHD1 inhibition: direct down-modulation of its catalytic activity, mediated by the same binding event that leads to SAMHD1 recruitment to the E3 ubiquitin ligase for proteasome-dependent degradation.
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