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The CRISPR effector Cam1 mediates membrane depolarization for phage defence
Christian F Baca1,2, You Yu3, Jakob T Rostøl1,4
1Laboratory of Bacteriology, The Rockefeller University, New York, NY, USA.
Nature
|January 10, 2024
Summary
Type III CRISPR-Cas systems use cyclic oligoadenylate-activated membrane protein 1 (Cam1) for defense. Cam1 triggers membrane depolarization and growth arrest, expanding our understanding of CRISPR immunity beyond nucleic acid degradation.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Prokaryotic type III CRISPR-Cas systems offer defense against foreign genetic elements.
- CRISPR-associated Rossman fold (CARF) proteins are key effectors in these systems.
- Some CARF proteins possess transmembrane helices and lack enzymatic activity, their function being unclear.
Purpose of the Study:
- To investigate the role of cyclic oligoadenylate-activated membrane protein 1 (Cam1) in type III CRISPR-Cas immunity.
- To elucidate the mechanism by which Cam1 contributes to cellular defense.
Main Methods:
- Structural and biochemical analyses of Cam1.
- In vivo studies to observe Cam1 localization and function.
- Assays to measure membrane potential and cell growth.
Main Results:
- Cam1 CARF domains bind cyclic tetra-adenylate second messengers.
- Cam1 localizes to the membrane and is predicted to form a tetrameric pore.
- Cam1 mediates defense against viral infection via membrane depolarization and growth arrest.
Conclusions:
- CRISPR-Cas immunity can involve cellular responses beyond nucleic acid degradation.
- Cam1 represents a novel class of CRISPR-Cas effectors utilizing membrane disruption for defense.
- This study expands the known repertoire of CRISPR-Cas immune mechanisms.
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