6XB5

Structure of Trichoplusia ni poxin in post-reactive state with Gp[2'-5']Ap[3']

Summary for 6XB5

• Entry DOI: 10.2210/pdb6xb5/pdb
• Descriptor: Poxin, 2',5'-GpAp (2 entities in total)
• Functional Keywords: poxin, nuclease, hdd13, lepidoptera, moth, butterfly, innate immunity, cgas, cgamp, sting, hydrolase
• Biological source: Trichoplusia ni
• Total number of polymer chains: 2
• Total formula weight: 55203.15

Authors

Eaglesham, J.B.,McCarty, K.L.,Kranzusch, P.J. (deposition date: 2020-06-05, release date: 2020-11-25, Last modification date: 2023-10-18)

Primary citation

Eaglesham, J.B.,McCarty, K.L.,Kranzusch, P.J.
Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host-pathogen conflict.
Elife, 9:-, 2020

PubMed Abstract: DNA viruses in the family encode poxin enzymes that degrade the immune second messenger 2'3'-cGAMP to inhibit cGAS-STING immunity in mammalian cells. The closest homologs of poxin exist in the genomes of insect viruses suggesting a key mechanism of cGAS-STING evasion may have evolved outside of mammalian biology. Here we use a biochemical and structural approach to discover a broad family of 369 poxins encoded in diverse viral and animal genomes and define a prominent role for 2'3'-cGAMP cleavage in metazoan host-pathogen conflict. Structures of insect poxins reveal unexpected homology to flavivirus proteases and enable identification of functional self-cleaving poxins in RNA-virus polyproteins. Our data suggest widespread 2'3'-cGAMP signaling in insect antiviral immunity and explain how a family of cGAS-STING evasion enzymes evolved from viral proteases through gain of secondary nuclease activity. Poxin acquisition by poxviruses demonstrates the importance of environmental connections in shaping evolution of mammalian pathogens.

PubMed: 33191912
DOI: 10.7554/eLife.59753

Experimental method

X-RAY DIFFRACTION (2.9 Å)