Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins

Article

关键词: GUIDED SURVEILLANCE COMPLEX;    CRYSTAL-STRUCTURE;    IMMUNE-SYSTEM;    RNA;    DNA;    RECOGNITION;    RESISTANCE;    SEQUENCE;    CASCADE;   

DOI  :  10.1038/nature15254

来源: SCIE

【 摘 要 】

The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive immune system that is one of the most widespread means by which bacteria defend themselves against phages(1-3). We identified the first examples of proteins produced by phages that inhibit a CRISPR-Cas system(4). Here we performed biochemical and in vivo investigations of three of these anti-CRISPR proteins, and show that each inhibits CRISPR-Cas activity through a distinct mechanism. Two block the DNA-binding activity of the CRISPR-Cas complex, yet do this by interacting with different protein subunits, and using steric or non-steric modes of inhibition. The third anti-CRISPR protein operates by binding to the Cas3 helicase-nuclease and preventing its recruitment to the DNA-bound CRISPR-Cas complex. In vivo, this anti-CRISPR can convert the CRISPR-Cas system into a transcriptional repressor, providing the first example-to our knowledge-of modulation of CRISPR-Cas activity by a protein interactor. The diverse sequences and mechanisms of action of these anti-CRISPR proteins imply an independent evolution, and foreshadow the existence of other means by which proteins may alter CRISPR-Cas function.

【 授权许可】

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