8GBE

Structure of a viral gasdermin protein A47 from Eptesipox virus

8GBE の概要

• エントリーDOI: 10.2210/pdb8gbe/pdb
• 分子名称: Protein A47 (2 entities in total)
• 機能のキーワード: viral mimicry, gasdermin, caspase, autoinhibition, pyroptosis, bats, immunity, cell death, immune system, viral protein
• 由来する生物種: Eptesipox virus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23802.73

構造登録者

Johnson, A.G.,Kranzusch, P.J. (登録日: 2023-02-25, 公開日: 2023-03-15, 最終更新日: 2024-05-22)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.46 Å)