Wiedenheft, B. Lander, G.C. Zhou, K. Jore, M.M. Brouns, S.J.J. Van Der Oost, J. Doudna, J.A. Doudna, J.A. text xx 9999 monographic und

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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 5-2 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. NUCLEIC ACID PROTEIN CASA PROTEIN CASB PROTEIN CASC PROTEIN CASD PROTEIN CASE RIBONUCLEOPROTEIN RNA UNCLASSIFIED DRUG https://drive.google.com/file/d/127a8PBRy3Qyv2txdjpG_7COpneyzf-uE/view?usp=drivesdk https://drive.google.com/file/d/127a8PBRy3Qyv2txdjpG_7COpneyzf-uE/view?usp=drivesdk 250602 20260521091516.0