Structures of the CRISPR-Cmr complex reveal mode of RNA target positioning

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Science  01 May 2015:
Vol. 348, Issue 6234, pp. 581-585
DOI: 10.1126/science.aaa4535

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Changing shape to destroy RNA

Clustered regularly interspaced short palindromic repeats (CRISPRs) together with CRISPR-associated (Cas) proteins form an adaptive immune system that helps bacteria and archaea defend themselves against invading viruses and plasmids. CRISPR RNAs (crRNAs) target CRISPR-Cas protein complexes to the invaders, bringing about their destruction. Taylor et al. used cryo–electron microscopy to determine the structure of a 12-subunit CRISPR-Cas protein complex with crRNA from Thermus thermophilus, in the presence and absence of single-stranded target RNA. Binding to the target RNA causes a change in shape of the CRISPR-Cas complex that results in target recognition and destruction.

Science, this issue p. 581


Adaptive immunity in bacteria involves RNA-guided surveillance complexes that use CRISPR (clustered regularly interspaced short palindromic repeats)–associated (Cas) proteins together with CRISPR RNAs (crRNAs) to target invasive nucleic acids for degradation. Whereas type I and type II CRISPR-Cas surveillance complexes target double-stranded DNA, type III complexes target single-stranded RNA. Near-atomic resolution cryo–electron microscopy reconstructions of native type III Cmr (CRISPR RAMP module) complexes in the absence and presence of target RNA reveal a helical protein arrangement that positions the crRNA for substrate binding. Thumblike β hairpins intercalate between segments of duplexed crRNA:target RNA to facilitate cleavage of the target at 6-nucleotide intervals. The Cmr complex is architecturally similar to the type I CRISPR-Cascade complex, suggesting divergent evolution of these immune systems from a common ancestor.

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