Structure of Gcn1 bound to stalled and colliding 80S ribosomes.

How a protein interacts with colliding ribosomes

31 August 2021

The structure of a protein at the head of a critical cellular stress response allows it to interact with two ribosomes at the same time.

Ribosomes are cellular factories that synthesize proteins based on the instructions given by RNA. Increasingly, collisions between ribosomes are thought to set off various stress responses in cells, including the integrated stress response, which pauses protein synthesis and has been implicated in various diseases including cancer and dementia.

Now, a team led by researchers at Universität Hamburg has investigated the structure of a key protein in the integrated stress response — the ribosome-binding protein Gcn1 — and how it interacts with two colliding ribosomes.

Their structural analysis showed how the one Gcn1 protein simultaneously interacts with both the leading stalled ribosome and the ribosome coming up behind it.

This information will help to inform ways to regulate the activation of Gcn2 — the protein that Gnc1 activates in the integrated stress response.

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References

1. PNAS 118, e2022756118 (2021). doi: 10.1073/pnas.2022756118