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Structures of the Cmr-β Complex Reveal the Regulation of the Immunity Mechanism of Type III-B CRISPR-Cas.

Sofos N, Feng M, Stella S, Pape T, Fuglsang A, Lin J, Huang Q, Li Y, She Q, Montoya G
Mol Cell 79 741-757.e7 (2020)
Related entries: 6s6b, 6s8b, 6s8e, 6s91, 6sh8, 6shb

Cited: 24 times
EuropePMC logo PMID: 32730741

Abstract

Cmr-β is a type III-B CRISPR-Cas complex that, upon target RNA recognition, unleashes a multifaceted immune response against invading genetic elements, including single-stranded DNA (ssDNA) cleavage, cyclic oligoadenylate synthesis, and also a unique UA-specific single-stranded RNA (ssRNA) hydrolysis by the Cmr2 subunit. Here, we present the structure-function relationship of Cmr-β, unveiling how binding of the target RNA regulates the Cmr2 activities. Cryoelectron microscopy (cryo-EM) analysis revealed the unique subunit architecture of Cmr-β and captured the complex in different conformational stages of the immune response, including the non-cognate and cognate target-RNA-bound complexes. The binding of the target RNA induces a conformational change of Cmr2, which together with the complementation between the 5' tag in the CRISPR RNAs (crRNA) and the 3' antitag of the target RNA activate different configurations in a unique loop of the Cmr3 subunit, which acts as an allosteric sensor signaling the self- versus non-self-recognition. These findings highlight the diverse defense strategies of type III complexes.

Reviews citing this publication (7)

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  2. Bacterial origins of cyclic nucleotide-activated antiviral immune signaling. Patel DJ, Yu Y, Jia N. Mol Cell 82 4591-4610 (2022)
  3. Digging into the lesser-known aspects of CRISPR biology. Guzmán NM, Esquerra-Ruvira B, Mojica FJM. Int Microbiol 24 473-498 (2021)
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  6. The Cyclic Oligoadenylate Signaling Pathway of Type III CRISPR-Cas Systems. Huang F, Zhu B. Front Microbiol 11 602789 (2020)
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Articles citing this publication (17)

  1. Intrinsic signal amplification by type III CRISPR-Cas systems provides a sequence-specific SARS-CoV-2 diagnostic. Santiago-Frangos A, Hall LN, Nemudraia A, Nemudryi A, Krishna P, Wiegand T, Wilkinson RA, Snyder DT, Hedges JF, Cicha C, Lee HH, Graham A, Jutila MA, Taylor MP, Wiedenheft B. Cell Rep Med 2 100319 (2021)
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  3. SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation. Steens JA, Zhu Y, Taylor DW, Bravo JPK, Prinsen SHP, Schoen CD, Keijser BJF, Ossendrijver M, Hofstra LM, Brouns SJJ, Shinkai A, van der Oost J, Staals RHJ. Nat Commun 12 5033 (2021)
  4. Cyclic oligoadenylate signalling and regulation by ring nucleases during type III CRISPR defence. Athukoralage JS, White MF. RNA rna.078739.121 (2021)
  5. Structure of a type IV CRISPR-Cas ribonucleoprotein complex. Zhou Y, Bravo JPK, Taylor HN, Steens JA, Jackson RN, Staals RHJ, Taylor DW. iScience 24 102201 (2021)
  6. A type III-A CRISPR-Cas system mediates co-transcriptional DNA cleavage at the transcriptional bubbles in close proximity to active effectors. Lin J, Shen Y, Ni J, She Q. Nucleic Acids Res 49 7628-7643 (2021)
  7. Structure and function of a bacterial type III-E CRISPR-Cas7-11 complex. Yu G, Wang X, Zhang Y, An Q, Wen Y, Li X, Yin H, Deng Z, Zhang H. Nat Microbiol 7 2078-2088 (2022)
  8. Cryo-EM structure and protease activity of the type III-E CRISPR-Cas effector. Huo Y, Zhao H, Dong Q, Jiang T. Nat Microbiol 8 522-532 (2023)
  9. Functional and Phylogenetic Diversity of Cas10 Proteins. Wiegand T, Wilkinson R, Santiago-Frangos A, Lynes M, Hatzenpichler R, Wiedenheft B. CRISPR J 6 152-162 (2023)
  10. Inactivation of Target RNA Cleavage of a III-B CRISPR-Cas System Induces Robust Autoimmunity in Saccharolobus islandicus. Zhang Y, Lin J, Tian X, Wang Y, Zhao R, Wu C, Wang X, Zhao P, Bi X, Yu Z, Han W, Peng N, Liang YX, She Q. Int J Mol Sci 23 8515 (2022)
  11. Molecular mechanism of allosteric activation of the CRISPR ribonuclease Csm6 by cyclic tetra-adenylate. Du L, Zhu Q, Lin Z. EMBO J 43 304-315 (2024)
  12. Reprogramming CRISPR-Mediated RNA Interference for Silencing of Essential Genes in Sulfolobales. Wimmer E, Zink IA, Schleper C. Methods Mol Biol 2522 177-201 (2022)
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  14. Structural rearrangements allow nucleic acid discrimination by type I-D Cascade. Schwartz EA, McBride TM, Bravo JPK, Wrapp D, Fineran PC, Fagerlund RD, Taylor DW. Nat Commun 13 2829 (2022)
  15. Structure of the Saccharolobus solfataricus type III-D CRISPR effector. Cannone G, Kompaniiets D, Graham S, White MF, Spagnolo L. Curr Res Struct Biol 5 100098 (2023)
  16. Target RNA-guided protease activity in type III-E CRISPR-Cas system. Wang X, Yu G, Wen Y, An Q, Li X, Liao F, Lian C, Zhang K, Yin H, Wei Y, Deng Z, Zhang H. Nucleic Acids Res 50 12913-12923 (2022)
  17. The structure of a Type III-A CRISPR-Cas effector complex reveals conserved and idiosyncratic contacts to target RNA and crRNA among Type III-A systems. Paraan M, Nasef M, Chou-Zheng L, Khweis SA, Schoeffler AJ, Hatoum-Aslan A, Stagg SM, Dunkle JA. PLoS One 18 e0287461 (2023)


Related citations provided by authors (1)

  1. Structures of the Cmr-beta Complex Reveal the Regulation of the Immunity Mechanism of Type III-B CRISPR-Cas. Sofos N, Feng M, Stella S, Pape T, Fuglsang A, Lin J, Huang Q, Li Y, She Q, Montoya G Biorxiv - (2020)

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