In cells, this organization enables highly efficient elimination of cellular DNA, conferring bacterial immunity against plasmids and phages via abortive infection

Unlike SPARDA, we predict that SPARHA forms a chain of HNH domains with double active sites

RNA-guide dependent target recognition induces conformational rearrangements in pAgo, causing significant shifts in the sensor loops SL1 and SL2, which in turn drive the connector loop (CL) forward and enable interactions with neighboring monomers

Our SPARHA story is out in Nature Communications!
doi.org/10.1038/s414...
We investigated a new short pAgo-HNH defense system, showing that it assembles into filaments degrading cellular DNA, inducing abortive infection, resolved their structure, and uncovered the activation mechanism 🧵

SPARHA represents a two-component defense system based on a suicidal cellular response, in which activation of the HNH effector by the pAgo sensor leads to filament formation, promoting efficient degradation of invading nucleic acids.

In cells, SPARHA is activated in the presence of invaders, cleaving cellular DNA and conferring protection to the bacterial population via an abortive infection mechanism.

Target DNA recognition induces conformational changes of SPARHA, freeing the HNH domains and promoting their dimerization. Subsequent association of HNH dimers leads to formation of right-handed HNH-pAgo filaments containing dimeric active sites capable of double-stranded DNA cleavage.