Evidence map›Paper›PMID 34850143›Full record

ArticleNucleic acids research2021

Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases.

Rafael Molina, Anne Louise Grøn Jensen, Javier Marchena-Hurtado, Blanca López-Méndez, Stefano Stella, Guillermo Montoya

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

14 citing papers in PubMed, 21 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

6 authors at 1 institution in 1 country.

Rafael MolinaStructural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B, Copenhagen, 2200, Denmark.
Anne Louise Grøn JensenStructural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B, Copenhagen, 2200, Denmark.
Javier Marchena-HurtadoStructural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B, Copenhagen, 2200, Denmark.
Blanca López-MéndezThe Novo Nordisk Foundation Center for Protein Research, Protein Structure & Function Programme, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Stefano StellaStructural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B, Copenhagen, 2200, Denmark.ORCID 0000-0002-9078-4659
Guillermo MontoyaStructural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B, Copenhagen, 2200, Denmark.ORCID 0000-0002-8269-3941
University of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Type III CRISPR-Cas effector systems detect foreign RNA triggering DNA and RNA cleavage and synthesizing cyclic oligoadenylate molecules (cA) in their Cas10 subunit. cAs act as a second messenger activating auxiliary nucleases, leading to an indiscriminate RNA degradation that can end in cell dormancy or death. Standalone ring nucleases are CRISPR ancillary proteins which downregulate the strong immune response of Type III systems by degrading cA. These enzymes contain a CRISPR-associated Rossman-fold (CARF) domain, which binds and cleaves the cA molecule. Here, we present the structures of the standalone ring nuclease from Sulfolobus islandicus (Sis) 0811 in its apo and post-catalytic states. This enzyme is composed by a N-terminal CARF and a C-terminal wHTH domain. Sis0811 presents a phosphodiester hydrolysis metal-independent mechanism, which cleaves cA4 rings to generate linear adenylate species, thus reducing the levels of the second messenger and switching off the cell antiviral state. The structural and biochemical analysis revealed the coupling of a cork-screw conformational change with the positioning of key catalytic residues to proceed with cA4 phosphodiester hydrolysis in a non-concerted manner.

Indexed as

CRISPR-Cas SystemsAdenine NucleotidesBinding SitesBiocatalysisChromatography, LiquidCRISPR-Associated ProteinsCrystallography, X-RayEndonucleasesKineticsMass SpectrometryModels, MolecularMutationNucleotides, CyclicOligoribonucleotidesProtein DomainsSulfolobus solfataricus2',5'-oligoadenylateAdenine NucleotidesCRISPR-Associated ProteinsEndonucleasesNucleotides, CyclicOligoribonucleotides

Identifiers

PMID34850143
PMCPMC8643638
OpenAlexW3217092674

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.