1.A.147. The CRISPR Effector, an Ion Channel Protein, Cam1 (Cam1) Family
The CRISPR effector Cam1 mediates membrane depolarization for phage defence (Baca et al. 2024). Prokaryotic type III CRISPR-Cas systems provide immunity against viruses and plasmids using CRISPR-associated Rossman fold (CARF) protein effectors. Recognition of transcripts of these invaders with sequences that are complementary to CRISPR RNA guides leads to the production of cyclic oligoadenylate second messengers, which bind CARF domains and trigger the activity of an effector domain. Whereas most effectors degrade host and invader nucleic acids, some are predicted to contain TMSs without an enzymatic function. Whether and how these CARF-TMS fusion proteins facilitate the type III CRISPR-Cas immune response was studied by Baca et al, 2024. They investigated the role of cyclic oligoadenylate-activated membrane protein 1 (Cam1) during type III CRISPR immunity. Structural and biochemical analyses revealed that the CARF domains of a Cam1 dimer bind cyclic tetra-adenylate second messengers. In vivo, Cam1 localizes to the membrane, is predicted to form a tetrameric transmembrane pore, and provides defence against viral infection through the induction of membrane depolarization and growth arrest. These results reveal that CRISPR immunity does not always operate through the degradation of nucleic acids, but is instead mediated via a wider range of cellular responses (Baca et al. 2024).
References:
Cam1 - CRISPR effector, shown to depoloarized the cell when activated, protecting against phage infectiions (Baca et al. 2024). It is 206 aas long with 1 - 3 TMSs. The N-terminal TMS is very hydrophobic while the second and third possible TMSs are less so. See family description for details.
Cam1 of Entacmaea quadricolor (Bubble-tip sanemone) (Parasicyonis actinostolodes)
Uncharacterized TIGR02710 family CRISPR-associated protein of 569 aas and 1 N-terminal TMS.
UP of Candidatus Helarchaeota archaeon
Uncharacterized protein of 248 aas and1 N-terminal TMS.
UP of Thermodesulfovibrio islandicus
DUF6293 family protein of 112 aas and possibly 1 N-terminal TMS.
DUF6293 family protein of 212 aas and 1 N-terminal TMS.
DUF1887 family CARF protein of 371 aas and 0 or 1 N-terminal TMS.
DUF1887 family protein of Neisseria dentiae
TIGR02710 family CRISPR-associated protein of 478 aas and 1 - 4 TMSs. The region of homology with other members of the family is at the N-terminus of this protein.
TIGR2710 protein of Herpetosiphonaceae bacterium
Uncharacterized protein of 274 aas and 3 TMSs, 2 near the N-terminus and1 near the C-termnus.
UP of Thiohalocapsa sp.
DUF1887 family CARF protein of 386 aas with 1 N-terminal TMS and possibly 1 or 2 more TMSs.
DUF1887 protein of Dongiaceae bacterium
Uncharacterized protein VSS75_32315 of 259 aas and 2 N-terminal TMSs plus possibly one more TMS.
UP of Candidatus Parabeggiatoa sp.
Uncharacterized CRISPR-associated protein (Cas_Cas02710) of 216 aas with 2 N-terminal TMSs plus one more TMS to the right of the 2 N-terminal TMSs.
UP of uncultured archaeon