ArticleNature2014
Structural basis of lentiviral subversion of a cellular protein degradation pathway.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 135 citations in OpenAlex.
- Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026Review
- Deep learning-driven decoding of ubiquitination: from regulatory mechanisms to targeted protein degradation.Biology direct · 2026Review
- Self-Dimerization Induced Proximity Targeting Chimeras (SDIPTAC) Lead to DCAF1 Loss of Function and Inhibition of HIV Replication.Journal of medicinal chemistry · 2026Article
- Deciphering lentiviral Vpr/Vpx determinants required for HUSH and SAMHD1 antagonism highlights the molecular plasticity of these evolutionary conflicts.Journal of virology · 2025Article
- Inhibitors of SAMHD1 Obtained from Chemical Tethering to the Guanine Antiviral Acyclovir.Biochemistry · 2025Article
- HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.The Journal of general virology · 2025Review
- CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.Viruses · 2024Review
- Chemical Proteomics-Guided Discovery of Covalent Ligands for Cancer Proteins.Annual review of cancer biology · 2024Article
- Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis.Nature communications · 2024Article
- Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4Nature communications · 2024Article
- Article
- DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance.Nature communications · 2024Article
- E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.Viruses · 2023Review
- Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.ACS medicinal chemistry letters · 2023Article
- Discovery of a Novel DCAF1 Ligand Using a Drug-Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets.Journal of chemical information and modeling · 2023Article
- Attenuation of reverse transcriptase facilitates SAMHD1 restriction of HIV-1 in cycling cells.Retrovirology · 2023Article
- Targeting SAMHD1: To overcome multiple anti-cancer drugs resistance in hematological malignancies.Genes & diseases · 2023Review
- Structural mechanism of CRL4-instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor.The EMBO journal · 2023Article
- Analysis of Tau/Nucleoporin Interactions by Surface Plasmon Resonance Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Targeted Protein Degradation by Electrophilic PROTACs that Stereoselectively and Site-Specifically Engage DCAF1.Journal of the American Chemical Society · 2022Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.