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Structural and Mechanistic Analyses Reveal a Unique Cas4-like Protein in the Mimivirus Virophage Resistance Element System.


ABSTRACT: A clustered regularly interspaced short palindromic repeats (CRISPR)-like "mimivirus virophage resistance element" (MIMIVIRE) system, which contains specific cascade genes and a CRISPR array against virophages, was reported in mimiviruses. An essential component of the MIMIVIRE system is R354, encoding a nuclease and a likely functional homolog of Cas4. Here we show that R354 is a dual nuclease with both exonuclease and endonuclease activities. Structural analysis revealed that the catalytic core domain of R354 is similar to those of Cas4 and ? exonuclease despite their low sequence identity. R354 forms a homodimer that is important for its exonuclease but not endonuclease activity. Structural comparisons between the active and semi-active states of R354 demonstrated that an activation loop adjacent to the catalytic site is critical for enzymatic activity. Overall, the results suggest that R354 belongs to a novel MIMIVIRE system involved in innate virus immunity and provides a template for the identification of new CRISPR systems in other species.

SUBMITTER: Dou C 

PROVIDER: S-EPMC6137704 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Structural and Mechanistic Analyses Reveal a Unique Cas4-like Protein in the Mimivirus Virophage Resistance Element System.

Dou Chao C   Yu Mingjing M   Gu Yijun Y   Wang Jinjing J   Yin Kun K   Nie Chunlai C   Zhu Xiaofeng X   Qi Shiqian S   Wei Yuquan Y   Cheng Wei W  

iScience 20180411


A clustered regularly interspaced short palindromic repeats (CRISPR)-like "mimivirus virophage resistance element" (MIMIVIRE) system, which contains specific cascade genes and a CRISPR array against virophages, was reported in mimiviruses. An essential component of the MIMIVIRE system is R354, encoding a nuclease and a likely functional homolog of Cas4. Here we show that R354 is a dual nuclease with both exonuclease and endonuclease activities. Structural analysis revealed that the catalytic cor  ...[more]

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