Evidence map›Paper›PMID 38989619›Full record

ArticleNucleic acids research2024

Molecular basis for cA6 synthesis by a type III-A CRISPR-Cas enzyme and its conversion to cA4 production.

Hemant N Goswami, Fozieh Ahmadizadeh, Bing Wang, Doreen Addo-Yobo, Yu Zhao, A Carl Whittington, Huan He, Michael P Terns, Hong Li

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Structural mechanism of SAM-AMP and SAM-AMPNature communications · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Characterization of Five CRISPR Systems inInternational journal of molecular sciences · 2025
    Article
  7. Article
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

9 authors.

Hemant N GoswamiInstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.ORCID 0000-0003-4807-9187
Fozieh AhmadizadehInstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Bing WangInstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Doreen Addo-YoboDepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA.
Yu ZhaoInstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
A Carl WhittingtonDepartment of Biological Sciences, Florida State University, Tallahassee, FL 32306, USA.
Huan HeInstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Michael P TernsBiochemistry and Molecular Biology, Genetics and Microbiology, University of Georgia, Athens, GA 30602, USA.ORCID 0000-0001-8330-1789
Hong LiInstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.ORCID 0000-0003-2046-9861

Funding

CRISPR Capture, Destroy, and Counter-Attack MechanismsR35GM118160 · NIGMS · UNIVERSITY OF GEORGIA · PI TERNS, MICHAEL P · 2016 to 2025
$5.8M
The Southeastern Center for Microscopy of Macromolecular Machines (SECM4)R24GM145964 · NIGMS · FLORIDA STATE UNIVERSITY · PI SCOTT M STAGG · 2022 to 2026
$5.5M
The Southeastern Consortium for Microscopy of MacroMolecular MachinesU24GM116788 · NIGMS · FLORIDA STATE UNIVERSITY · PI AGBANDJE-MCKENNA, MAVIS, BULLITT, ESTHER · 2016 to 2020
$4.6M
Structures of RNA Processing and Silencing Enzymes in ProkaryotesR01GM099604 · NIGMS · FLORIDA STATE UNIVERSITY · PI LI, HONG · 2012 to 2023
$3.3M
Purchase of a FEI Titan Krios for 3-D EMS10RR025080 · NCRR · FLORIDA STATE UNIVERSITY · PI TAYLOR, KENNETH ALLEN · 2008 to 2008
$2.0M
Mechanisms and Applications of RNA-mediated Enzymes in Translation and ImmunityR35GM152081 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI Hong Li · 2024 to 2026
$1.8M
CryoEM Equipment Enhancements for Florida State UniversityS10RR024564 · NCRR · FLORIDA STATE UNIVERSITY · PI TAYLOR, KENNETH ALLEN · 2008 to 2008
$178k
NCRR NIH HHS S10 RR024564NCRR NIH HHS S10 RR025080NIGMS NIH HHS R01 GM099604NIGMS NIH HHS R24 GM145964NIGMS NIH HHS R35 GM118160NIGMS NIH HHS R35 GM152081NIGMS NIH HHS U24 GM116788NIH HHS R35 GM152081
6 · The paper itself

Abstract

The type III-A (Csm) CRISPR-Cas systems are multi-subunit and multipronged prokaryotic enzymes in guarding the hosts against viral invaders. Beyond cleaving activator RNA transcripts, Csm confers two additional activities: shredding single-stranded DNA and synthesizing cyclic oligoadenylates (cOAs) by the Cas10 subunit. Known Cas10 enzymes exhibit a fascinating diversity in cOA production. Three major forms-cA3, cA4 and cA6have been identified, each with the potential to trigger unique downstream effects. Whereas the mechanism for cOA-dependent activation is well characterized, the molecular basis for synthesizing different cOA isoforms remains unclear. Here, we present structural characterization of a cA6-producing Csm complex during its activation by an activator RNA. Analysis of the captured intermediates of cA6 synthesis suggests a 3'-to-5' nucleotidyl transferring process. Three primary adenine binding sites can be identified along the chain elongation path, including a unique tyrosine-threonine dyad found only in the cA6-producing Cas10. Consistently, disrupting the tyrosine-threonine dyad specifically impaired cA6 production while promoting cA4 production. These findings suggest that Cas10 utilizes a unique enzymatic mechanism for forming the phosphodiester bond and has evolved distinct strategies to regulate the cOA chain length.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsAdenine NucleotidesBacterial ProteinsBinding SitesModels, MolecularOligoribonucleotidesAdenine NucleotidesBacterial ProteinsCRISPR-Associated ProteinsOligoribonucleotides

Identifiers

PMID38989619
PMCPMC11417356

What OpenQuestion holds

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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.