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

Wiedenheft, Blake ; Lander, Gabriel C ; Zhou, Kaihong ; Jore, Matthijs M ; Brouns, Stan JJ ; van der Oost, John ; Doudna, Jennifer A ; Nogales, Eva

Nature, 2011-09, Vol.477 (7365), p.486-489

eScholarship, University of California

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  • Título:
    Structures of the RNA-guided surveillance complex from a bacterial immune system
  • Autor: Wiedenheft, Blake ; Lander, Gabriel C ; Zhou, Kaihong ; Jore, Matthijs M ; Brouns, Stan JJ ; van der Oost, John ; Doudna, Jennifer A ; Nogales, Eva
  • Assuntos: Bacterial ; Base Pairing ; Biochemistry and Cell Biology ; Biological ; Biological Sciences ; Cryoelectron Microscopy ; Escherichia coli K12 ; Escherichia coli Proteins ; General Science & Technology ; Genetics ; Inverted Repeat Sequences ; Macromolecular Substances ; Molecular ; Protein Conformation ; RNA
  • É parte de: Nature, 2011-09, Vol.477 (7365), p.486-489
  • Notas: Nature, vol 477, iss 7365
    486 - 489
  • Descrição: 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.
  • Editor: eScholarship, University of California
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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