Decoding the molecular interplay in the central dogma: An overview of mass spectrometry‐based methods to investigate protein‐metabolite interactions

Abstract

With the emergence of next‐generation nucleotide sequencing and mass spectrometry‐based proteomics and metabolomics tools, we have comprehensive and scalable methods to analyze the genes, transcripts, proteins, and metabolites of a multitude of biological systems. Despite the fascinating new molecular insights at the genome, transcriptome, proteome and metabolome scale, we are still far from fully understanding cellular organization, cell cycles and biology at the molecular level. Significant advances in sensitivity and depth for both sequencing as well as mass spectrometry‐based methods allow the analysis at the single cell and single molecule level. At the same time, new tools are emerging that enable the investigation of molecular interactions throughout the central dogma of molecular biology. In this review, we provide an overview of established and recently developed mass spectrometry‐based tools to probe metabolite‐protein interactions—from individual interaction pairs to interactions at the proteome‐metabolome scale.

Differentiating specific and non-specific protein-metabolite interactions using gradient open port probe electrospray ionization mass spectrometry

“…1 A variety of techniques have been reported to study PMIs 2 , including surface plasmon resonance spectroscopy, isothermal titration calorimetry, nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry (ESI-MS). [3][4][5][6] Unlike other methods, mass spectrometry has valuable advantages such as high sensitivity, high-speed analysis, low sample consumption, little-to-no sample preparation, etc., which make it a routine tool for protein analysis. Methods for studying PMIs based on MS can be roughly classified into two categories: metabolitecentric and protein-centric approaches.…”