What is it about?

All cells in our body contain the enzyme Gcn2. Gcn2 helps the cell to better cope with nutrient starvation. To carry out its functions, Gcn2 must be in direct contact with the protein Gcn1. We used a genetic approach to find potential Gcn2 contact points in Gcn1. According to this approach, four amino acids in Gcn1 are important for Gcn2 binding. In addition, a different set of amino acids – when mutated - may make the binding to Gcn2 even stronger.

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Why is it important?

The way how Gcn2 monitors nutrient availability is still a large mystery. Our findings on how Gcn2 binds to its activator protein Gcn1 brings us a step further in filling this large gap of knowledge. Since nutrients are important to fuel any biological process in the cell, it is not surprising that Gcn2 is implicated in many biological functions. When Gcn2 does not work properly it can lead to diseases (e.g. cancer, dementia, or diabetes). For example, cancer cells take advantage of Gcn2 to help fuel their excessive nutritional demands. Getting detailed insight into how exactly Gcn2 works, will allow the discovery of novel and more effective treatment measures, followed by the development of new drugs to treat these diseases.


This work was an exciting journey that took many years. It started with the development of a new method (published this year) and continued with the execution of experiments involving students from New Zealand, Germany and France. This work has opened up opportunities for many more studies, student projects, and collaborations, to continue generating more scientific knowledge. This is what makes science so exciting and rewarding.

Evelyn Sattlegger
Massey University

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This page is a summary of: A genetic approach to identify amino acids in Gcn1 required for Gcn2 activation, PLoS ONE, November 2022, PLOS, DOI: 10.1371/journal.pone.0277648.
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