Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T.; Raczkowski, Ashleigh M.; Fox, Tara; Earl, Lesley A.; Patel, Dinshaw J.; Subramaniam, Sriram

doi:10.1016/j.cell.2017.09.006

Title: Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex

Journal Article · Thu Oct 05 00:00:00 EDT 2017 · Cell

DOI:https://doi.org/10.1016/j.cell.2017.09.006· OSTI ID:1430317

Guo, Tai Wei ^[1]; Bartesaghi, Alberto ^[1]; Yang, Hui ^[2]; Falconieri, Veronica ^[1]; Rao, Prashant ^[1]; Merk, Alan ^[1]; Eng, Edward T. ^[3]; Raczkowski, Ashleigh M. ^[3]; Fox, Tara ^[4]; Earl, Lesley A. ^[1]; Patel, Dinshaw J. ^[2]; Subramaniam, Sriram ^[1]

National Inst. of Health (NIH), Bethesda, MD (United States)
Memorial Sloan Kettering Cancer Center, New York, NY (United States)
New York Structural Biology Center, New York, NY (United States)
National Inst. of Health (NIH), Bethesda, MD (United States); Frederick National Lab. for Cancer Research, MD (United States)

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. Here, a central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Inst. of Health; Memorial Sloan Kettering Cancer Center; Center for Cancer Research, National Cancer Inst.; Simons Foundation; Agouron Inst.

Grant/Contract Number:: HHSN261200800001E; P30CA008748; GM104962; 349247; GM103310; F00316; S10 Od019994-01

OSTI ID:: 1430317

Journal Information:: Cell, Vol. 171, Issue 2; ISSN 0092-8674

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 108 works

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Title: Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex

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