Cross-talk and integrative post-translational modifications

Si Wu; Lindsay Pino

doi:10.1039/D2MO90036J

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DOI: 10.1039/D2MO90036J (Editorial) Mol. Omics, 2023, 19, 93-94

Cross-talk and integrative post-translational modifications

Si Wu *^a and Lindsay Pino ^b
^aDepartment of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73012, USA. E-mail: si.wu@ou.edu; lpino@talus.bio; Fax: +1-405-325-6111
^bTalus Bioscience, Seattle, WA 98122, USA

Received 21st December 2022 , Accepted 21st December 2022

Si Wu

Lindsay Pino

The human genome project revealed that there are approximately 20 [thin space (1/6-em)]

000 protein encoding genes in the human genome, much fewer than the number previously predicted. Rather, it was found that protein structural and functional diversity goes far beyond the genome and is largely due to allelic variation, alternative splicing, and post-translational modification (PTM). As bioanalytical techniques have been developed that have improved the depth and accuracy of molecular profiling, particularly with respect to analysis of proteoforms with PTMs, it has become clear that PTMs regulate protein function and/or participate in cellular signalling in nearly every known biological pathway. Furthermore, changes to PTMs or misfunction of enzymes responsible for the catalytic addition or removal of PTMs are known to cause many human diseases.

As such, the study of the effect of protein structure on signalling pathways, protein–protein interactions, protein–DNA/RNA interactions, PTM crosstalk, and overall proteostasis is of particular interest. While many PTMs have been functionally annotated, the function of most PTMs is not currently known. As the pathways involved in intracellular interactomes and intercellular communication are unimaginably complex, the question of how to approach the omics-based investigation of biological signalling pathways, spatiotemporal dynamics, and proteostasis becomes critical.

In this themed issue of Molecular Omics on cross-talk and integrative post-translational modifications, authors have contributed manuscripts that utilize and discuss cutting-edge approaches to the analysis of protein interactions, PTMs, and signalling pathways. We found that an interesting commonality among these manuscripts was the diverse use of mass spectrometry-based proteomics to study PTM expression and protein interactions. Several authors implemented chemical crosslinking mass spectrometry (XL-MS) methods to study interactomes resulting in the identification of many previously unknown protein interactions. Others used top-down and bottom-up MS-based proteomics methods to explore global differences in proteoforms and PTMs (e.g., N-glycosylation and phosphorylation). Also included is an insightful review article that discusses methods for MS investigation of O-GlcNAcylation and outlooks for improving the methodology for the study of this biologically relevant PTM.

This themed issue features a selection of articles aimed at highlighting current state-of-the-art techniques as well as novel methods for quantitative and qualitative analysis of proteoforms, PTMs, and protein interactions. From these articles, it is clear that MS-based proteomics methods are rapidly growing and changing to be applicable to this intensely important research area. Overall, it is clear that the use of MS-based omics to study cross-talk and PTMs is an area of research that is rich in opportunities for application, method development, and data analysis. The publications included in this themed issue of Molecular Omics are just a few examples of the innovation and improvements currently being undertaken. We hope that this issue will shed light on the methods that allow us to delve into the complicated protein interaction networks and inspire researchers to tackle this important issue.