Gergő Gógl The puzzle of protein interactions

Small motifs, big effects: protein interactions 

Proteins are molecules with a specific structure and function in the cell, determined by their chemical composition and physical interactions with other proteins. The vast majority of these interactions are mediated by what are known as “short linear interaction motifs”. 

These motifs, consisting of 5 to 10 of protein building blocks (amino acids), are found in the so-called “disordered” regions of proteins, i.e. regions that lack a stable structure. The distinctive feature of these motifs is that they mediate transient interactions between proteins. Their sequence is highly conserved throughout evolution, and mutations in these motifs are often associated with diseases, highlighting their biological importance.

Tackling the study of orphan protein motifs 

The number and sequence of these binding motifs have been predicted using various computational approaches. However, to date, few of them have known partners or a clearly established role in the cell, making them “orphan” motifs. Indeed, the brevity of their interactions makes them particularly difficult to study. 

Gergő Gógl has developed an innovative method, called nHU, which makes it possible to study the interactions of these orphan motifs, even the most fleeting ones. Unlike other methods, this approach is capable of measuring tens of thousands of interactions mediated by orphan motifs with great sensitivity and precision. It can also be applied to whole proteins under conditions similar to those observed in the cell. Everything needed to study orphan motifs!

Deciphering large-scale protein interactions: the ambition of the Impulscience project 

With the support of Impulscience, Gergő Gógl and his team will use the nHU method to identify the partners of orphan motifs, validate that these interactions occur between native proteins, and determine under what conditions they take place in the cell. They will also analyse the impact of mutations on these motifs, which are associated with many diseases including cancer, on cellular functions. 

Overall, this project will adopt a revolutionary quantitative and biophysical approach capable of answering questions that have remained unanswered for years: what are the partners of these orphan motifs, which are so essential from a biological point of view, and how can we study the mechanisms they orchestrate?