8GBE

Structure of a viral gasdermin protein A47 from Eptesipox virus

Summary for 8GBE

• Entry DOI: 10.2210/pdb8gbe/pdb
• Descriptor: Protein A47 (2 entities in total)
• Functional Keywords: viral mimicry, gasdermin, caspase, autoinhibition, pyroptosis, bats, immunity, cell death, immune system, viral protein
• Biological source: Eptesipox virus
• Total number of polymer chains: 1
• Total formula weight: 23802.73

Authors

Johnson, A.G.,Kranzusch, P.J. (deposition date: 2023-02-25, release date: 2023-03-15, Last modification date: 2024-05-22)

Primary citation

Boys, I.N.,Johnson, A.G.,Quinlan, M.,Kranzusch, P.J.,Elde, N.C.
Structural homology screens reveal poxvirus-encoded proteins impacting inflammasome-mediated defenses.
Biorxiv, 2023

PubMed Abstract: Viruses acquire host genes via horizontal gene transfer and can express them to manipulate host biology during infections. Some viral and host homologs retain sequence identity, but evolutionary divergence can obscure host origins. We used structural modeling to compare vaccinia virus proteins with metazoan proteomes. We identified vaccinia as a homolog of gasdermins, the executioners of pyroptosis. An X-ray crystal structure of A47 confirmed this homology and cell-based assays revealed that A47 inhibits pyroptosis. We also identified vaccinia as the product of a cryptic gene fusion event coupling a Bcl-2 related fold with a pyrin domain. C1 associates with components of the inflammasome, a cytosolic innate immune sensor involved in pyroptosis, yet paradoxically enhances inflammasome activity, suggesting a benefit to poxvirus replication in some circumstances. Our findings demonstrate the potential of structural homology screens to reveal genes that viruses capture from hosts and repurpose to benefit viral fitness.

PubMed: 36909515
DOI: 10.1101/2023.02.26.529821

Experimental method

X-RAY DIFFRACTION (1.46 Å)