Evidence map›Paper›PMID 26101257›Full record

ArticleNucleic acids research2015

SAMHD1 is a single-stranded nucleic acid binding protein with no active site-associated nuclease activity.

Kyle J Seamon, Zhiqiang Sun, Luda S Shlyakhtenko, Yuri L Lyubchenko, James T Stivers

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
8.9field-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

86 citing papers in PubMed, 129 citations in OpenAlex.

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26 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

5 authors at 4 institutions in 1 country.

Kyle J SeamonDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Zhiqiang SunDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Luda S ShlyakhtenkoDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Yuri L LyubchenkoDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA.
James T StiversDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA jstivers@jhmi.edu.
Nebraska Medical Center · USJohns Hopkins Medicine · USJohns Hopkins University · USUniversity of Nebraska Medical Center · US

Funding

Structural Characterization of APOBECS's Atomic interactionsP01GM091743 · NIGMS · UNIVERSITY OF MINNESOTA · PI HARRIS, REUBEN S · 2011 to 2015
$10.1M
Uracil Damage Recognition by Uracil DNA GlyocosylaseR01GM056834 · NIGMS · UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE · PI STIVERS, JAMES T. · 1998 to 2021
$8.3M
PHARMACOLOGY TRAINING GRANTT32GM008763 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI FREEL MEYERS, CAREN L. · 2000 to 2019
$6.1M
Protein Self-Assembly into NanoaggregatesR01GM096039 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI LYUBCHENKO, YURI L · 2011 to 2018
$2.9M
NIGMS NIH HHS P01 GM091743NIGMS NIH HHS R01 GM056834NIGMS NIH HHS R01GM056834NIGMS NIH HHS R01 GM096039NIGMS NIH HHS T32 GM008763
6 · The paper itself

Abstract

The HIV-1 restriction factor SAMHD1 is a tetrameric enzyme activated by guanine nucleotides with dNTP triphosphate hydrolase activity (dNTPase). In addition to this established activity, there have been a series of conflicting reports as to whether the enzyme also possesses single-stranded DNA and/or RNA 3'-5' exonuclease activity. SAMHD1 was purified using three chromatography steps, over which the DNase activity was largely separated from the dNTPase activity, but the RNase activity persisted. Surprisingly, we found that catalytic and nucleotide activator site mutants of SAMHD1 with no dNTPase activity retained the exonuclease activities. Thus, the exonuclease activity cannot be associated with any known dNTP binding site. Monomeric SAMHD1 was found to bind preferentially to single-stranded RNA, while the tetrameric form required for dNTPase action bound weakly. ssRNA binding, but not ssDNA, induces higher-order oligomeric states that are distinct from the tetrameric form that binds dNTPs. We conclude that the trace exonuclease activities detected in SAMHD1 preparations arise from persistent contaminants that co-purify with SAMHD1 and not from the HD active site. An in vivo model is suggested where SAMHD1 alternates between the mutually exclusive functions of ssRNA binding and dNTP hydrolysis depending on dNTP pool levels and the presence of viral ssRNA.

Indexed as

Catalytic DomainDNA-Binding ProteinsDNA, Single-StrandedExodeoxyribonucleasesExoribonucleasesHumansMonomeric GTP-Binding ProteinsMutationNucleoside-TriphosphataseProtein BindingProtein MultimerizationProtein Structure, TertiaryRNA-Binding ProteinsSAM Domain and HD Domain-Containing Protein 1ZincDNA-Binding ProteinsDNA, Single-StrandedExodeoxyribonucleasesExoribonucleasesMonomeric GTP-Binding ProteinsNucleoside-TriphosphataseRNA-Binding ProteinsSAM Domain and HD Domain-Containing Protein 1SAMHD1 protein, humanZinc

Identifiers

PMID26101257
PMCPMC4513882
OpenAlexW2131403247

What OpenQuestion holds

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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.