Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense

cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are signaling proteins that initiate antiviral immunity in animal cells and cyclic-oligonucleotide-based anti-phage signaling system (CBASS) phage defense in bacteria. Upon phage recognition, bacterial CD-NTases catalyze synthesis of cyclic-oligonucleotide signals, which activate downstream effectors and execute cell death. How CD-NTases control nucleotide selection to specifically induce defense remains poorly defined. Here, we combine structural and nucleotide-analog interference-mapping approaches to identify molecular rules controlling CD-NTase specificity. Structures of the cyclic trinucleotide synthase Enterobacter cloacae CdnD reveal coordinating nucleotide interactions and a possible role for inverted nucleobase positioning during product synthesis. We demonstrate that correct nucleotide selection in the CD-NTase donor pocket results in the formation of a thermostable-protein-nucleotide complex, and we extend our analysis to establish specific patterns governing selectivity for each of the major bacterial CD-NTase clades A&ndash;H. Our results explain CD-NTase specificity and enable predictions of nucleotide second-messenger signals within diverse antiviral systems. &nbsp;</p

Importance of green receptivity in Euglossa tridentata (Hymenoptera: Apidae) foraging behavior

This study experimentally tests the visual discrimination ability of Euglossa tridentata with three colored mazes. A black and white maze represented total contrast, and served as a null model to compare the ability of E. tridentata to distinguish colors in a green and white maze, and a maze designed after the orchid Sobralia lindleyana. Test bees behaved as predicted in the Green-White maze where the mean completion time was significantly longer than each other maze. This indicates Hymenopteran green photoreceptors are relatively insensitive in foraging. Although the null model was predicted to be the easiest color combination to distinguish, the maze based on S. lindleyana’s floral colors had a significantly shorter mean completion time. This suggests that bee vision has evolved to distinguish color sets that indicate the location of resources, and not optimal vision to be able to discriminate between all colors and patterns. The experimental data support “Exaptation Theory” as the most valid model describing the role of green receptivity in Hymenopteran foraging behavior. Este estudio probó experimentalmente la habilidad de discriminación visual de Euglossa tridentata con tres laberintos de colores diferentes. Un laberinto blanquinegro representó el contraste total, y sirvió como un modelo nulo para comparar la habilidad de E. tridentata para distinguir los colores en un laberinto verde y blanco y en un laberinto diseñado para asemejar a la orquidea Sobralia lindleyana. Las abejas observadas se comportaron como se predijo en el laberinto verdiblanco, donde el tiempo de terminación promedio fue significativamente más largo que en los otros laberintos. Esto indica que el fotorreceptor para el color verde en himenópteros es relativamente insensible en forrajeo. Aunque se predijo que el modelo nulo sería la combinación de colores más fácil de distinguir, el laberinto basado en los colores florales de S. lindleyana tuvo un tiempo de terminación promedio significativamente más corto. Esto sugiere que la visión de las abejas ha evolucionado para distinguir las combinaciones de color que indican la ubicación de recursos, y no la visión óptima para ser capaces de discriminar entre todos los colores y modelos. Las observaciones experimentales de datos apoyan “La Teoría de Exaptación” como el modelo más válido para describir el papel de la receptividad verde en el comportamiento de forrajeo de los himenópteros.https://digitalcommons.usf.edu/tropical_ecology/1499/thumbnail.jp

Importance of green receptivity in Euglossa tridentata (Hymenoptera: Apidae) foraging behavior

This study experimentally tests the visual discrimination ability of Euglossa tridentata with three colored mazes. A black and white maze represented total contrast, and served as a null model to compare the ability of E. tridentata to distinguish colors in a green and white maze, and a maze designed after the orchid Sobralia lindleyana. Test bees behaved as predicted in the Green-White maze where the mean completion time was significantly longer than each other maze. This indicates Hymenopteran green photoreceptors are relatively insensitive in foraging. Although the null model was predicted to be the easiest color combination to distinguish, the maze based on S. lindleyana’s floral colors had a significantly shorter mean completion time. This suggests that bee vision has evolved to distinguish color sets that indicate the location of resources, and not optimal vision to be able to discriminate between all colors and patterns. The experimental data support “Exaptation Theory” as the most valid model describing the role of green receptivity in Hymenopteran foraging behavior. Este estudio probó experimentalmente la habilidad de discriminación visual de Euglossa tridentata con tres laberintos de colores diferentes. Un laberinto blanquinegro representó el contraste total, y sirvió como un modelo nulo para comparar la habilidad de E. tridentata para distinguir los colores en un laberinto verde y blanco y en un laberinto diseñado para asemejar a la orquidea Sobralia lindleyana. Las abejas observadas se comportaron como se predijo en el laberinto verdiblanco, donde el tiempo de terminación promedio fue significativamente más largo que en los otros laberintos. Esto indica que el fotorreceptor para el color verde en himenópteros es relativamente insensible en forrajeo. Aunque se predijo que el modelo nulo sería la combinación de colores más fácil de distinguir, el laberinto basado en los colores florales de S. lindleyana tuvo un tiempo de terminación promedio significativamente más corto. Esto sugiere que la visión de las abejas ha evolucionado para distinguir las combinaciones de color que indican la ubicación de recursos, y no la visión óptima para ser capaces de discriminar entre todos los colores y modelos. Las observaciones experimentales de datos apoyan “La Teoría de Exaptación” como el modelo más válido para describir el papel de la receptividad verde en el comportamiento de forrajeo de los himenópteros.https://digitalcommons.usf.edu/tropical_ecology/1499/thumbnail.jp

Tracing the evolutionary origins of antiviral immunity.

Animal and bacterial cells use shared mechanisms to defend against viruses. Analyzing 3 families of immune genes, a new study in PLOS Biology illuminates this evolutionary connection and traces the emergence of antiviral signaling across domains of life

Structure of Human cGAS Reveals a Conserved Family of Second-Messenger Enzymes in Innate Immunity

Innate immune recognition of foreign nucleic acids induces protective interferon responses. Detection of cytosolic DNA triggers downstream immune signaling through activation of cyclic GMP-AMP synthase (cGAS). We report here the crystal structure of human cGAS, revealing an unanticipated zinc-ribbon DNA-binding domain appended to a core enzymatic nucleotidyltransferase scaffold. The catalytic core of cGAS is structurally homologous to the RNA-sensing enzyme, 2′-5′ oligo-adenylate synthase (OAS), and divergent C-terminal domains account for specific ligand-activation requirements of each enzyme. We show that the cGAS zinc ribbon is essential for STING-dependent induction of the interferon response and that conserved amino acids displayed within the intervening loops are required for efficient cytosolic DNA recognition. These results demonstrate that cGAS and OAS define a family of innate immunity sensors and that structural divergence from a core nucleotidyltransferase enables second-messenger responses to distinct foreign nucleic acids