Poxvirus portal complex structure identifies three key proteins and enzyme docking
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Researchers from the Crick Institute have determined the structure of the poxvirus portal complex, a channel in the viral core responsible for releasing genetic material. Published in Nature, the cryo-electron tomography and AlphaFold2 analysis identified three essential proteins and showed how a DNA-release enzyme docks onto the complex. The findings resolve how poxviruses export mRNA and DNA sequentially during infection.
Cryo-ET and AI-Driven Protein Mapping
Tom Calcraft in Peter Rosenthal's lab used cryo-electron tomography to obtain a 'map' of the portal complex in vaccinia virus. Then, with Miguel Hernandez Gonzalez from Michael Way's lab, they used AlphaFold2 to predict all viral protein structures and matched them to the map. This revealed three proteins—previously known to be essential for mRNA export—as components of the portal, with one also involved in assembling new virus particles. The analysis further showed that the viral enzyme responsible for DNA genome release docks directly onto the portal complex.
Central Replication Hub
The portal complex serves as a central hub coordinating two key steps of the poxvirus replication cycle. Initially, mRNA transcripts are exported through the portal to produce proteins that suppress host immune responses. Subsequently, the viral DNA genome is released to allow replication. The docking of the DNA-release enzyme on the portal confirms its role in orchestrating this sequential release. This finding integrates portal function with viral assembly and immune evasion.
What's Next
The Crick team plans to investigate how the portal complex can be targeted to develop new antiviral therapies against poxviruses, including mpox. It remains unclear whether portal complexes in other poxviruses share the same architecture or if they could be disrupted without harming host cells.
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Poxvirus portal complex structure identifies three key proteins and enzyme docking


