Grapevine

Filament structure found to activate and regulate CRISPR-Cas 'protein scissors'

CRISPR-Cas systems help to protect bacteria from viruses. Several different types of CRISPR-Cas defense systems are found in bacteria, which differ in their composition and functions. Among them, the most studied proteins today are Cas9 and Cas12, also known as DNA or "gene scissors," which have revolutionized the field of genome editing, enabling scientists to edit genomes and correct disease-causing mutations precisely.

Researchers from the Institute of Biotechnology at the Life Sciences Center of Vilnius University—Dalia Smalakytė, Audronė Rukšėnaitė, Dr. Giedrius Sasnauskas, Dr. Giedrė Tamulaitienė, and Dr. Gintautas Tamulaitis—have revealed the structure of the CRISPR-Cas protein scissors found in bacteria and provided mechanistic details on how they function. The results of their study have been published in Molecular Cell.

A team of researchers led by Dr. Tamulaitis is studying the bacterial defense system CRISPR-Cas10, which acts as a sensor. When a virus attacks the bacterium, it sends a "message" by synthesizing unique signal molecules called cyclic oligoadenylates.

These signaling molecules are recognized by different effectors, i.e. accessory proteins in the system that enhance the bacterial defense against viruses. A recent computational analysis predicted that CRISPR-Cas10 effectors may have diverse enzymatic activities, allowing bacteria to defend themselves against viruses in multiple ways.

"The discovery of cyclic oligoadenylates and the understanding of the mechanism of CRISPR-Cas10 have sparked great scientific interest and a breakthrough in signaling pathway research. Recently, a similar protection principle has been identified in other bacterial defense systems: CBASS, Pycsar, and Thoeris. In this study, we investigated the tripartite CalpL-CalpT-CalpS effector which is activated by CRISPR-Cas10 signaling molecules and we explained how this complex system works and how it is regulated," explains Dr. Tamulaitis.