Immunology

For many bacteria, one line of defense against viral infection is the CRISPR-Cas system. At the center of this system is a surveillance complex that recognizes viral DNA and triggers its destruction. However, viruses can fight back and disable this surveillance complex by using anti-CRISPR proteins. For the first time, researchers have solved, using a high-resolution imaging technique called cryo-electron microscopy, the structure of viral anti-CRISPR proteins attached to a bacterial CRISPR surveillance complex, revealing precisely how viruses neutralize the bacterial defense system. The research team found that the anti-CRISPR proteins act by locking down CRISPR's ability to identify and attack the viral genome. The proteins within the complex wrap around the CRISPR RNA exposing specific sections of bacterial RNA. One type of anti-CRISPR protein covers the exposed section of CRISPR RNA, preventing the CRISPR system from scanning the viral DNA. Based on its location and negative charge, an anti-CRISPR protein acts as a DNA mimic, fooling CRISPR into binding this immobilizing protein, rather than invading viral DNA. The researchers believe that this new understanding of anti-CRISPR proteins could eventually lead to more sophisticated and effective tools for gene editing.