Happy Tuesday! We hope you’re having a good start to your week so far.
Today, we’d like to highlight an interesting study that was published in Cell journal by the group of Prof. Paola Picotti at ETH Zurich titled: A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication.
A Short Summary
The study describes the limited proteolysis (LiP) method to assess proteome-wide binding to metabolites and uncovers new allosteric and enzymatic functions. It demonstrates that LiP is a powerful tool to investigate drug targets in the native cellular environment.
Background on the Study
Interactions between proteins and small molecules control a variety of cellular processes including signaling, metabolism, and protein translation. Thus, playing a major role in maintaining cellular homeostasis.
However, our knowledge of the metabolite-protein interaction is limited due to the challenge of identifying metabolite-protein interactions in an unbiased way.
How The Problem Was Addressed
The LiP* technology that was used in this study has recently raised considerable interest in the field because it is one of the few methods that enables the unbiased and proteome-wide profiling of protein conformational changes resulting from interaction of proteins with compounds.
It’s not limited to these applications, however, and has been used for other stimuli such as thermal shifts, protein-protein interactions, and posttranslational modifications.
The Magic Behind The Science
The underlying principle is the same for all stimuli: Conformational changes affect the kinetics of the proteolytic cleavage with an unspecific protease. If a compound causes this change, it will show up as a quantitative difference in peptides in the part of the protein where the change happened. The peptides derived from the proteolysis can be quantified with mass spectrometry.
The authors of this study show that the LiP approach enables identification of a network of known and novel metabolite-protein interactions and associated binding sites in selected biological matrix.
Read the entire publication here.
*The limited Proteolysis (LiP) technology was developed and patented by the group of Prof. Paola Picotti at ETH Zurich and is exclusively licensed to Biognosys. Biognosys is currently developing applications of the LiP technology for proteome wide identification of proteins that bind to small molecules (e.g. for drug target deconvolution).