ABSTRACT
Many organisms have evolved specialized immune pattern-recognition receptors, including nucleotide-binding oligomerization domain-like receptors (NLRs) of the STAND superfamily that are ubiquitous in plants, animals, and fungi. Although the roles of NLRs in eukaryotic immunity are well established, it is unknown whether prokaryotes use similar defense mechanisms. Here, we show that antiviral STAND (Avs) homologs in bacteria and archaea detect hallmark viral proteins, triggering Avs tetramerization and the activation of diverse N-terminal effector domains, including DNA endonucleases, to abrogate infection. Cryo-electron microscopy reveals that Avs sensor domains recognize conserved folds, active-site residues, and enzyme ligands, allowing a single Avs receptor to detect a wide variety of viruses. These findings extend the paradigm of pattern recognition of pathogen-specific proteins across all three domains of life.
Subject(s)
Archaea , Archaeal Proteins , Bacteria , Bacterial Proteins , Immunity, Innate , NLR Proteins , Receptors, Pattern Recognition , Viral Proteins , Animals , Archaea/immunology , Archaea/virology , Archaeal Proteins/chemistry , Archaeal Proteins/classification , Archaeal Proteins/genetics , Bacteria/immunology , Bacteria/virology , Bacterial Proteins/chemistry , Bacterial Proteins/classification , Bacterial Proteins/genetics , Bacteriophages , Cryoelectron Microscopy , NLR Proteins/chemistry , NLR Proteins/genetics , Phylogeny , Receptors, Pattern Recognition/chemistry , Receptors, Pattern Recognition/classification , Receptors, Pattern Recognition/genetics , Viral Proteins/chemistry , Viral Proteins/geneticsABSTRACT
Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential.
