Viruses that infect bacteria (bacteriophages) are the most abundant biological entity on earth, causing more than10^23 infections every second. As a result of this predation, prokaryotes have evolved diverse defense systems, including CRISPRs (Clustered Regularly Interspersed Short Palindromic Repeat), which use RNA-guided protein complexes to seek and destroy viral nucleic acids, blocking infection. In response, bacteriophages have evolved countermeasures called Anti-CRISPR (Acr) proteins that block host immunity and rescue infection. Acrs are diverse and studies suggest that there is a unique Acr adapted to block most, if not all subclasses of CRISPR systems. Here we present our investigation of a novel Acr that inhibits a Type I-E CRISPR complex termed CASCADE. To provide a molecular understanding of how AcrIE9 blocks CASCADE-mediated defense, we have employed Cryo-Electron Microscopy (Cryo-EM), a cutting-edge structural biology technique.
