Structural Biology

Seahorse Versus Pathogen

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Science  06 May 2011:
Vol. 332, Issue 6030, pp. 643
DOI: 10.1126/science.332.6030.643-c
CREDIT: JORE ET AL., NAT. STRUCT. MOL. BIOL. 18, 10.1038/NSMB.2019 (2011)

Just like us, prokaryotes—bacteria and archea—must also protect themselves against pathogenic microbes, such as viruses and plasmids. Prokaryotes use the CRISPR (clustered regularly interspaced short palindromic repeats) system, an adaptive immune response whereby sequence snippets from the invading pathogen's genome are collected and stored by the host, which then uses them to target the pathogen for destruction.

Jore et al. have analyzed the composition and low-resolution structure of the Cascade complex, which lies at the heart of the CRISPR immune response. The snippets of invader sequence are transcribed and converted into CRISPR RNA (crRNA), which is bound by the Cascade complex. Thus loaded, the Cascade complex is able to bind sequences complementary to the crRNA either as double-stranded (ds) DNA or single-stranded DNA. With a dsDNA target, Cascade-complex binding displaced the noncomplementary target strand as an R loop, in an ATP-independent reaction. The overall structure of the Cascade complex surprisingly resembled the shape of a seahorse, with the spine and head consisting of a tightly curved polymer of six CasC protein subunits, which might bind the crRNA.

Nat. Struct. Mol. Biol. 18, 10.1038/nsmb.2019 (2011).

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