Evidence map›Paper›PMID 37710013›Full record

ArticleNature structural & molecular biology2023

Structure reveals why genome folding is necessary for site-specific integration of foreign DNA into CRISPR arrays.

Andrew Santiago-Frangos, William S Henriques, Tanner Wiegand, Colin C Gauvin, Murat Buyukyoruk, Ava B Graham, Royce A Wilkinson, Lenny Triem, Kasahun Neselu, Edward T Eng and 2 more

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

8 citing papers in PubMed, 15 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

12 authors at 3 institutions in 1 country.

Andrew Santiago-FrangosDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA.ORCID 0000-0001-9615-065X
William S HenriquesDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA.
Tanner WiegandDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA.ORCID 0000-0002-0528-268X
Colin C GauvinDepartment of Chemistry and Biochemistry, Montana State University, Bozeman, MT, USA.ORCID 0000-0001-7171-552X
Murat BuyukyorukDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA.
Ava B GrahamDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA.
Royce A WilkinsonDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA.
Lenny TriemDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA.
Kasahun NeseluSimons Electron Microscopy Center, National Resource for Automated Molecular Microscopy, New York Structural Biology Center, New York, NY, USA.
Edward T EngSimons Electron Microscopy Center, National Resource for Automated Molecular Microscopy, New York Structural Biology Center, New York, NY, USA.ORCID 0000-0002-8014-7269
Gabriel C LanderDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-4921-1135
Blake WiedenheftDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT, USA. bwiedenheft@gmail.com.ORCID 0000-0001-9297-5304
Montana State University · USNew York Structural Biology Center · USScripps Research Institute · US

Funding

Research Core (Developmental Research Project Program)P20GM103474 · NIGMS · MONTANA STATE UNIVERSITY - BOZEMAN · PI Ann Therese Bertagnolli · 2012 to 2026
$60.0M
NCCAT: National Center for CryoEM Access and Training- Supplement for Windows 10 and FFIU24GM129539 · NIGMS · NEW YORK STRUCTURAL BIOLOGY CENTER · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2018 to 2023
$53.9M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
Structural and functional understanding of bacterial defense and viral counter defenseR35GM134867 · NIGMS · MONTANA STATE UNIVERSITY - BOZEMAN · PI Blake A Wiedenheft · 2020 to 2026
$3.8M
Mechanisms of CRISPR-mediated immunity and applications beyond editingK99GM147842 · NIGMS · MONTANA STATE UNIVERSITY - BOZEMAN · PI SANTIAGO-FRANGOS, ANDREW · 2022 to 2023
$171k
NIGMS NIH HHS K99 GM147842NIGMS NIH HHS P20 GM103474NIGMS NIH HHS R01 GM129325NIGMS NIH HHS R35 GM134867NIGMS NIH HHS U24 GM129539
6 · The paper itself

Abstract

Bacteria and archaea acquire resistance to viruses and plasmids by integrating fragments of foreign DNA into the first repeat of a CRISPR array. However, the mechanism of site-specific integration remains poorly understood. Here, we determine a 560-kDa integration complex structure that explains how Pseudomonas aeruginosa Cas (Cas1-Cas2/3) and non-Cas proteins (for example, integration host factor) fold 150 base pairs of host DNA into a U-shaped bend and a loop that protrude from Cas1-2/3 at right angles. The U-shaped bend traps foreign DNA on one face of the Cas1-2/3 integrase, while the loop places the first CRISPR repeat in the Cas1 active site. Both Cas3 proteins rotate 100 degrees to expose DNA-binding sites on either side of the Cas2 homodimer, which each bind an inverted repeat motif in the leader. Leader sequence motifs direct Cas1-2/3-mediated integration to diverse repeat sequences that have a 5'-GT. Collectively, this work reveals new DNA-binding surfaces on Cas2 that are critical for DNA folding and site-specific delivery of foreign DNA.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsBinding SitesCRISPR-Cas SystemsDNAPlasmidsCRISPR-Associated ProteinsDNA

Identifiers

PMID37710013
PMCPMC10872659
OpenAlexW4386741046

What OpenQuestion holds

Textmetadata
LicenceTDM
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.