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Structural highlights

Function

CSE1_ECOLI CRISPR (clustered regularly interspaced short palindromic repeat), is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).^{[1] [2] [3] [4]} A component of Cascade, which participates in CRISPR interference, the third stage of CRISPR immunity. Cascade binds both crRNA and in a sequence-specific manner negatively supercoiled dsDNA target. This leads to the formation of an R-loop in which the crRNA binds the target DNA, displacing the noncomplementary strand. Cas3 is recruited to Cascade, probably via interactions with CasA, nicks target DNA and then unwinds and cleaves the target, leading to DNA degradation and invader neutralization. CasA is not required for formation of Cascade, but probably enhances binding to and subsequent recognition of both target dsDNA and ssDNA.^{[5] [6] [7] [8]}

See Also

• CRISPR type I-E (Cascade)
• CRISPR-Cas
• CRISPR-Cas Part II
• Endonuclease 3D structures

References

1. ↑ Perez-Rodriguez R, Haitjema C, Huang Q, Nam KH, Bernardis S, Ke A, DeLisa MP. Envelope stress is a trigger of CRISPR RNA-mediated DNA silencing in Escherichia coli. Mol Microbiol. 2011 Feb;79(3):584-99. doi: 10.1111/j.1365-2958.2010.07482.x. Epub, 2010 Dec 13. PMID:21255106 doi:10.1111/j.1365-2958.2010.07482.x
2. ↑ Jore MM, Lundgren M, van Duijn E, Bultema JB, Westra ER, Waghmare SP, Wiedenheft B, Pul U, Wurm R, Wagner R, Beijer MR, Barendregt A, Zhou K, Snijders AP, Dickman MJ, Doudna JA, Boekema EJ, Heck AJ, van der Oost J, Brouns SJ. Structural basis for CRISPR RNA-guided DNA recognition by Cascade. Nat Struct Mol Biol. 2011 May;18(5):529-36. doi: 10.1038/nsmb.2019. Epub 2011 Apr, 3. PMID:21460843 doi:http://dx.doi.org/10.1038/nsmb.2019
3. ↑ Mulepati S, Orr A, Bailey S. Crystal structure of the largest subunit of a bacterial RNA-guided immune complex and its role in DNA target binding. J Biol Chem. 2012 May 23. PMID:22621933 doi:10.1074/jbc.C112.379503
4. ↑ Sashital DG, Wiedenheft B, Doudna JA. Mechanism of Foreign DNA Selection in a Bacterial Adaptive Immune System. Mol Cell. 2012 Apr 17. PMID:22521690 doi:10.1016/j.molcel.2012.03.020
5. ↑ Perez-Rodriguez R, Haitjema C, Huang Q, Nam KH, Bernardis S, Ke A, DeLisa MP. Envelope stress is a trigger of CRISPR RNA-mediated DNA silencing in Escherichia coli. Mol Microbiol. 2011 Feb;79(3):584-99. doi: 10.1111/j.1365-2958.2010.07482.x. Epub, 2010 Dec 13. PMID:21255106 doi:10.1111/j.1365-2958.2010.07482.x
6. ↑ Jore MM, Lundgren M, van Duijn E, Bultema JB, Westra ER, Waghmare SP, Wiedenheft B, Pul U, Wurm R, Wagner R, Beijer MR, Barendregt A, Zhou K, Snijders AP, Dickman MJ, Doudna JA, Boekema EJ, Heck AJ, van der Oost J, Brouns SJ. Structural basis for CRISPR RNA-guided DNA recognition by Cascade. Nat Struct Mol Biol. 2011 May;18(5):529-36. doi: 10.1038/nsmb.2019. Epub 2011 Apr, 3. PMID:21460843 doi:http://dx.doi.org/10.1038/nsmb.2019
7. ↑ Mulepati S, Orr A, Bailey S. Crystal structure of the largest subunit of a bacterial RNA-guided immune complex and its role in DNA target binding. J Biol Chem. 2012 May 23. PMID:22621933 doi:10.1074/jbc.C112.379503
8. ↑ Sashital DG, Wiedenheft B, Doudna JA. Mechanism of Foreign DNA Selection in a Bacterial Adaptive Immune System. Mol Cell. 2012 Apr 17. PMID:22521690 doi:10.1016/j.molcel.2012.03.020
9. ↑ Mulepati S, Heroux A, Bailey S. Crystal structure of a CRISPR RNA-guided surveillance complex bound to a ssDNA target. Science. 2014 Aug 14. pii: 1256996. PMID:25123481 doi:http://dx.doi.org/10.1126/science.1256996