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Tetramerization and RNA-guided filament assembly control Schlafen-Argonaute antiphage defense

Two deeply conserved protein families, Argonaute (Ago) and Schlafen (SLFN), play defense roles in diverse prokaryotes and eukaryotes, including humans. Here, we identify a monophyletic group of proteins broadly distributed across bacteria and archaea that fuse a SLFN domain with an Ago core and a GHKL-family ATPase. Using SLFN-pAgo from Runella zeae as a model, we show that these proteins protect bacterial cells against bacteriophages by employing the Ago core as a guide-dependent sensor and...

bioRxiv 11d ago

Zinc Tolerance Through Glutathione Import Strikes a Fine Balance Between Protection and Damage in Streptococcus mutans

Recently, our group showed that the dental pathogen Streptococcus mutans is inherently more tolerant to high zinc stress than other streptococci, a phenotype associated with the presence of a P-type ATPase exporter named ZccE, virtually unique to S. mutans. In addition to zccE, a previous transcriptome analysis revealed that S. mutans upregulates genes involved in glutathione uptake during initial exposure to zinc stress. Glutathione, a major supplier of organic sulfur that also plays key...

bioRxiv 8d ago

The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor

{beta}-cardiac myosin is the primary motor protein in the human heart responsible for force generation by converting chemical energy from ATP hydrolysis to mechanical work. It binds actin, produces force through its powerstroke, and releases actin, and must complete this cycle several times a second within each heartbeat. Like other muscle myosins, cardiac myosin has a low duty ratio of ~5%, the fraction of time in the actin-bound force-producing state.

bioRxiv 4d ago

DNA remodeling couples target recognition to directional transposition in a Tn7-like CAST

CRISPR-associated transposons (CASTs) couple target recognition to the insertion of large DNA cargoes, but how distinct targeting pathways are converted into productive and directional integration remains poorly understood1. Here we define the assembly pathway of a type I-B1 CAST from Anabaena variabilis, a system closely related to prototypical Tn7 that retains TnsD-mediated glmS recognition while incorporating CRISPR-based RNA-guided targeting2. Cryo-electron microscopy structures across...

bioRxiv 7d ago