Researchers from Vilnius University have unveiled the fascinating structure and mechanism of the CRISPR-Cas protein scissors, shedding light on how these molecular tools protect bacteria from viral attacks. This discovery paves the way for their potential application as sensitive infection indicators. Learn more about the complex signaling pathways and regulation of these CRISPR-Cas systems, which have revolutionized genome editing.
Smart Filament Architecture
The CRISPR-Cas system is an extraordinary bacterial defense mechanism that has stunned the research realm. At the center of this system are the ‘protein scissors’ named as Cas9 and Cas12, which has turned around the genome editing science.
Researchers at Vilnius University have now demonstrated the detailed architecture and mechanism of action of another element in this defense system – CRISPR-Cas10 effector. In response to viral attack by the virus of a bacterium cyclical oligoadenylates, which are a special type of signal molecules, are synthesized. The CRISPR-Cas10 effector that recognizes these molecules is made up of three essential proteins, CalpL, CalpS, and CalpT.
A Tightly Regulated Dance
By performing biochemical, biophysical, bacterial survivability assays and cryo-EM for the first time in this effector, they revealed the mechanism governing function of CRISPR-Cas10.
The researchers discovered that the CalpL protein binds to the signaling molecules and ooze into a polymeric filament structure. This thread arrests the CalpT-CalpS hetereodimer in a correct site where active centre of scissors of CalpL and its coupling-with inhibitor of calpain, the Calpt-T. Once CalpT is cleaved, the CalpS protein can be released and it will start regulating gene expression to aid calprotectin in inhibiting virus.
Applications Unleashed
The ultimate control of the activity of these CRISPR-Cas protein scissors is one of the most exciting things we found here. Researchers have discovered an internal timer in the signaling molecules and filaments that begins to beat as soon as they group together. This is in contrast to other related signal-sensing effector proteins, which lack this function, the authors noted.
Gary Kasson at the National Institute of Allergy and Infectious Diseases says: The new insights into how complex the CRISPR-Cas10 system is “sets us up for really practical applications”: using the controlled protein scissors as a diagnostic from infection. It could have major consequences in many different areas, including health through to biosecurity. The more researchers learn about this bacterial defense, the more surprises they will find as we continue to push the boundaries of science.
