Structural biology of CRISPR–Cas immunity and genome editing enzymes

CRISPR–Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, we examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR–Cas immune systems and deployed for wide-ranging genome editing applications. We explore the adaptive and interference aspects of CRISPR–Cas function as well as open questions about the molecular mechanisms responsible for genome targeting. These structural insights reflect close evolutionary links between CRISPR–Cas systems and mobile genetic elements, including the origins and evolution of CRISPR–Cas systems from DNA transposons, retrotransposons and toxin–antitoxin modules. We discuss how the evolution and structural diversity of CRISPR–Cas systems explain their functional complexity and utility as genome editing tools.