Sounding the Antiviral Alarm - Biosciences Area

At the cellular level, as a virus invades, its DNA or RNA trigger immune responses in the healthy host cells. How this process is triggered and a better understanding of the specific enzymes involved is still being defined. Researchers at Harvard Medical School and a collaboration across multiple X-ray facilities, including the Berkeley Center for Structural Biology beamlines at the Advanced Light Source (ALS), compared the human and insect enzymes involved in this process. They used protein crystallography to closely examine the structures, and learned that although overall function is similar, each group of organisms has a slightly different DNA-binding surface and resulting molecular immune response.

In humans, the immune sensor cGAS detects viral DNA and produces the signaling molecule 2′3′-cGAMP, which turns on antiviral immunity. A parallel pathway exists in flies, where cGLR1 senses RNA and synthesizes 3′2′-cGAMP, a new but similar molecule to humans, to activate immunity. cGAS-like receptors are a diverse new family of immune proteins that remain mostly uncharacterized.

This effort was supported in part by the ALS-ENABLE program.