Evidence map›Paper›PMID 26431200›Full record

ArticlePLoS pathogens2015

Phospho-dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis and Restriction.

Laurence H Arnold, Harriet C T Groom, Simone Kunzelmann, David Schwefel, Sarah J Caswell, Paula Ordonez, Melanie C Mann, Sabrina Rueschenbaum, David C Goldstone, Simon Pennell and 5 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Article
  3. Transition metal activation reframes SAMHD1 regulation.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. SAMHD1 in cancer: curse or cure?Journal of molecular medicine (Berlin, Germany) · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Laurence H ArnoldThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Harriet C T GroomThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Simone KunzelmannThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
David SchwefelThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Sarah J CaswellThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Paula OrdonezThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Melanie C MannThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Sabrina RueschenbaumThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
David C GoldstoneThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Simon PennellThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Steven A HowellThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Jonathan P StoyeThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom; Faculty of Medicine, Imperial College London, London, United Kingdom.
Michelle WebbCentre for Genomic Medicine, Institute for Human Development, Faculty of Medicine and Human Sciences, University of Manchester, Manchester, United Kingdom.
Ian A TaylorThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
Kate N BishopThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, United Kingdom.
The Francis Crick Institute · GBUniversity of Manchester · GB

Funding

Medical Research Council MC_U117592729Medical Research Council U117512710Medical Research Council U117565647Medical Research Council U117592729Wellcome TrustWellcome Trust 084955
6 · The paper itself

Abstract

SAMHD1 restricts HIV-1 infection of myeloid-lineage and resting CD4+ T-cells. Most likely this occurs through deoxynucleoside triphosphate triphosphohydrolase activity that reduces cellular dNTP to a level where reverse transcriptase cannot function, although alternative mechanisms have been proposed recently. Here, we present combined structural and virological data demonstrating that in addition to allosteric activation and triphosphohydrolase activity, restriction correlates with the capacity of SAMHD1 to form "long-lived" enzymatically competent tetramers. Tetramer disruption invariably abolishes restriction but has varied effects on in vitro triphosphohydrolase activity. SAMHD1 phosphorylation also ablates restriction and tetramer formation but without affecting triphosphohydrolase steady-state kinetics. However phospho-SAMHD1 is unable to catalyse dNTP turnover under conditions of nucleotide depletion. Based on our findings we propose a model for phosphorylation-dependent regulation of SAMHD1 activity where dephosphorylation switches housekeeping SAMHD1 found in cycling cells to a high-activity stable tetrameric form that depletes and maintains low levels of dNTPs in differentiated cells.

Indexed as

BiocatalysisCell LineChromatography, GelChromatography, High Pressure LiquidCrystallography, X-RayFlow CytometryHIV-1HumansMonomeric GTP-Binding ProteinsPhosphorylationProtein ConformationReverse Transcriptase Polymerase Chain ReactionSAM Domain and HD Domain-Containing Protein 1Spectrophotometry, AtomicMonomeric GTP-Binding ProteinsSAM Domain and HD Domain-Containing Protein 1SAMHD1 protein, human

Identifiers

PMID26431200
PMCPMC4592219
OpenAlexW2261805883

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.