Evidence map›Paper›PMID 33531504›Full record

ArticleNature communications2021

Nucleic acid binding by SAMHD1 contributes to the antiretroviral activity and is enhanced by the GpsN modification.

Corey H Yu, Akash Bhattacharya, Mirjana Persaud, Alexander B Taylor, Zhonghua Wang, Angel Bulnes-Ramos, Joella Xu, Anastasia Selyutina, Alicia Martinez-Lopez, Kristin Cano and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 41 citations in OpenAlex.

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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 4 institutions in 2 countries.

Corey H YuDepartment of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.ORCID 0000-0002-1374-4194
Akash Bhattacharya *Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
Mirjana Persaud *Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Alexander B TaylorDepartment of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
Zhonghua WangDepartment of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
Angel Bulnes-RamosDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Joella XuDepartment of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.
Anastasia SelyutinaDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Alicia Martinez-LopezDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Kristin CanoDepartment of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
Borries DemelerDepartment of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB, Canada.
Baek KimDepartment of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.ORCID 0000-0001-7986-4335
Stephen C HardiesDepartment of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
Felipe Diaz-GrifferoDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA. felipe.diaz-griffero@einsteinmed.org.ORCID 0000-0002-7021-6152
Dmitri N IvanovDepartment of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA. ivanov@uthscsa.edu.ORCID 0000-0002-9442-3316
The University of Texas Health Science Center at San Antonio · USAlbert Einstein College of Medicine · USEmory University · USUniversity of Lethbridge · CA

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
Training in HIV/AIDS Pathogenesis; Basic and Translational ResearchT32AI007501 · NIAID · YESHIVA UNIVERSITY · PI PRASAD, VINAYAKA R. · 1995 to 2024
$6.6M
University of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1M
Lentivirus Replication Strategy and PathogenesisR01AI136581 · NIAID · EMORY UNIVERSITY · PI Baek Kim · 2018 to 2026
$3.9M
Development of an UltraScan Meta-Scheduler for HPC Job SubmissionR01GM120600 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Emre H. Brookes, BORRIES DEMELER · 2016 to 2026
$3.6M
Regulation of SAMHD1 antiviral activityR01AI150455 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI DIAZ-GRIFFERO, FELIPE · 2019 to 2024
$3.3M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Biochemistry of SAMHD1-mediated innate immunity responsesR01AI136697 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI IVANOV, DMITRI N · 2019 to 2022
$1.9M
Retroviral capsid recognition by TRIM5alpha restriction factorsR01AI104476 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI IVANOV, DMITRI N · 2014 to 2018
$1.8M
Biochemistry of SAMHD1-mediated innate immunity responsesR37AI136697 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DMITRI N IVANOV · 2024 to 2026
$1.7M
SAMHD1 controls dNTP pool and HIV sensitivity to NRTIsR01AI150451 · NIAID · EMORY UNIVERSITY · PI KIM, BAEK · 2019 to 2019
$311k
NCI NIH HHS P30 CA054174NIAID NIH HHS R01 AI104476NIAID NIH HHS R01 AI136581NIAID NIH HHS R01 AI136697NIAID NIH HHS R01 AI150451NIAID NIH HHS R01 AI150455NIAID NIH HHS R37 AI136697NIAID NIH HHS T32 AI007501NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM120600NIGMS NIH HHS R25 GM086262NIH HHS S10 OD021527
6 · The paper itself

Abstract

SAMHD1 impedes infection of myeloid cells and resting T lymphocytes by retroviruses, and the enzymatic activity of the protein-dephosphorylation of deoxynucleotide triphosphates (dNTPs)-implicates enzymatic dNTP depletion in innate antiviral immunity. Here we show that the allosteric binding sites of the enzyme are plastic and can accommodate oligonucleotides in place of the allosteric activators, GTP and dNTP. SAMHD1 displays a preference for oligonucleotides containing phosphorothioate bonds in the Rp configuration located 3' to G nucleotides (GpsN), the modification pattern that occurs in a mechanism of antiviral defense in prokaryotes. In the presence of GTP and dNTPs, binding of GpsN-containing oligonucleotides promotes formation of a distinct tetramer with mixed occupancy of the allosteric sites. Mutations that impair formation of the mixed-occupancy complex abolish the antiretroviral activity of SAMHD1, but not its ability to deplete dNTPs. The findings link nucleic acid binding to the antiretroviral activity of SAMHD1, shed light on the immunomodulatory effects of synthetic phosphorothioated oligonucleotides and raise questions about the role of nucleic acid phosphorothioation in human innate immunity.

Indexed as

HumansImmunity, InnateMutationNucleotidesOxidoreductases Acting on CH-CH Group DonorsSAM Domain and HD Domain-Containing Protein 1NucleotidesOxidoreductases Acting on CH-CH Group DonorsSAM Domain and HD Domain-Containing Protein 1SAMHD1 protein, humantrans-2-enoyl-CoA reductase (NADPH)

Identifiers

PMID33531504
PMCPMC7854603
OpenAlexW3127222994

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.