NLM DIR Seminar Schedule

Abstract:

Research into antiviral mechanisms in prokaryotic cells has contributed greatly to our understanding of the principles of immunity and virulence in the context of human health, while also producing extremely effective tools for DNA cloning and editing. Members of the YprA-like helicase family are present in abundant and recently described defense systems DISARM, Dpd, and Druantia, as well as DNA repair operons that confer antibiotic resistance. Phylogenetic, genomic neighborhood, and AlphaFold protein structure prediction analysis indicates these proteins are the result of remarkable adaptive radiation. Each of the known defense systems encodes phylogenetically distinct YprA homologs with complex, unique domain architectures not previously recognized. The analysis also reveals novel classes of some of these known systems as well as several major YprA-like branches that have not been reported, each with its own distinguishing features, which we denote ARMADA (DISARM-like antiviral defense array) systems. Previous work in our group focused in detail on CoCoNuT (coiled-coil nuclease tandem) predicted antiviral defense systems. Unexpectedly, we have determined during our analysis of the YprA-like family that Druantia Types II and IV encompass a fourth type of CoCoNuT system. AlphaFold analysis of these experimentally uncharacterized systems detected domains suggesting a complex restriction mechanism related to homing endonucleases, with the CoCoNuT-related factors predicted to contribute an additional RNA-targeting capability.