Evidence map›Paper›PMID 25856754›Full record

ArticleCell host & microbe2015

Molecular determinants for recognition of divergent SAMHD1 proteins by the lentiviral accessory protein Vpx.

David Schwefel, Virginie C Boucherit, Evangelos Christodoulou, Philip A Walker, Jonathan P Stoye, Kate N Bishop, Ian A Taylor

Open access · hybridAbstract read
In one paragraph

Article in Cell host & microbe, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 63 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

David SchwefelDivision of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Virginie C BoucheritDivision of Virology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Evangelos ChristodoulouDivision of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Philip A WalkerDivision of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Jonathan P StoyeDivision of Virology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK; Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
Kate N BishopDivision of Virology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Electronic address: kbishop@nimr.mrc.ac.uk.
Ian A TaylorDivision of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Electronic address: itaylor@nimr.mrc.ac.uk.
The Francis Crick Institute · GBMRC London Institute of Medical Sciences · GBNational Institute for Medical Research · TZ

Funding

Medical Research Council MC_U117592729Medical Research Council U117512710Medical Research Council U117565647Medical Research Council U117592729Wellcome TrustWellcome Trust 085955
6 · The paper itself

Abstract

The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation. We present the ternary complex of Vpx from SIV that infects mandrills (SIVmnd-2) with the cullin-4 substrate receptor, DCAF1, and N-terminal and SAM domains from mandrill SAMHD1. The structure reveals details of Vpx lineage-specific targeting of SAMHD1 N-terminal "degron" sequences. Comparison with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing Vpx lineages to N- or C-terminal SAMHD1 sequences. Inspection of the Vpx-DCAF1 interface also reveals conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein Vpr. These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to promote viral replication.

Indexed as

Host-Pathogen InteractionsProtein MultimerizationAnimalsCarrier ProteinsCrystallography, X-RayMandrillusModels, MolecularMonomeric GTP-Binding ProteinsProtein ConformationViral Regulatory and Accessory ProteinsVirus ReplicationCarrier ProteinsMonomeric GTP-Binding ProteinsViral Regulatory and Accessory ProteinsVPX protein, Simian immunodeficiency virus

Identifiers

PMID25856754
PMCPMC4400269
OpenAlexW2044387049

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.