Harnessing High-Resolution Mass Spectrometry and High-Performance Supercomputing for Broad-Range PTM Identification from Microorganisms

摘要

Many proteins in eukaryotic organisms, such as histones, are modified by multiple post-translational modifications (PTMs). However, the prevalence of such combinatorial PTMs in microorganisms is largely unknown. Combinatorial PTMs are known to act collectively to regulate protein activities. To study proteome-wide PTM interactions requires the ability to globally identity and quantify a broad range of PTMs. Here, we present a method combining high-resolution mass spectrometry with scalable parallel supercomputing on the Titan, currently the world's fastest supercomputer, to identify and quantify a broad range of PTMs, including oxidation, deamidation, citrullinat ion, hydroxylation, mono-, di-, and trimethylation, acetylation, phosphorylation, s-nitrosylation, nitration, methylthiolation from laboratory-grown E. coli and free-living microorganisms in a natural microbial community. We demonstrate an optimized high-performance mass spectrometry-based shotgun proteomics for the identification of a broad range of PTMs from microbial isolates and natural environmental communities.