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Nature. 2011 Sep 21;477(7365):486-489. doi: 10.1038/nature10402.

Structures of the RNA-guided surveillance complex from a bacterial immune system.

Author information

1
Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
2
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
3
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
4
Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands.
5
Department of Chemistry, University of California, Berkeley, California 94720, USA.
6
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
#
Contributed equally

Abstract

Bacteria and archaea acquire resistance to viruses and plasmids by integrating short fragments of foreign DNA into clustered regularly interspaced short palindromic repeats (CRISPRs). These repetitive loci maintain a genetic record of all prior encounters with foreign transgressors. CRISPRs are transcribed and the long primary transcript is processed into a library of short CRISPR-derived RNAs (crRNAs) that contain a unique sequence complementary to a foreign nucleic-acid challenger. In Escherichia coli, crRNAs are incorporated into a multisubunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defence), which is required for protection against bacteriophages. Here we use cryo-electron microscopy to determine the subnanometre structures of Cascade before and after binding to a target sequence. These structures reveal a sea-horse-shaped architecture in which the crRNA is displayed along a helical arrangement of protein subunits that protect the crRNA from degradation while maintaining its availability for base pairing. Cascade engages invading nucleic acids through high-affinity base-pairing interactions near the 5' end of the crRNA. Base pairing extends along the crRNA, resulting in a series of short helical segments that trigger a concerted conformational change. This conformational rearrangement may serve as a signal that recruits a trans-acting nuclease (Cas3) for destruction of invading nucleic-acid sequences.

PMID:
21938068
PMCID:
PMC4165517
DOI:
10.1038/nature10402
[Indexed for MEDLINE]
Free PMC Article
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