Proteins are the product of gene expression and allow cells to perform their functions: from structural proteins that control a cell's shape to kinases involved in signal transduction.
The process that leads from the genetic information encoded in the DNA to a protein comprises two steps, transcription and translation. Whereas transcriptional, post-transcriptional and translational regulation mainly affect the type and amount of proteins in the cell, a more subtle layer of control involves the modifications a protein can undergo after its synthesis. Protein Post-Translational Modifications (PTMs), the covalent addition or removal of chemical groups to or from the side chains of some amino acid residues, play a pivotal role in regulating the function, subcellular localization, or stability of a protein and are related to the development of several diseases (cancer, diabetes, neurodegenerative diseases).
Due to the inevitable impact of PTMs on protein mass, the utilization of Tandem Mass Spectrometry (MS/MS) has emerged as a popular strategy for their study. Mass spectrometers record the peptides' fragmentation spectra, which are fed to software called peptide search engines that compare them to theoretical spectra generated by simulating in silico the fragmentation process. One advantage of MS/MS is that it is unbiased and thus can theoretically detect any mass shift (PTM) present on a peptide. In practice, researchers face various limitations: the low abundance of several PTMs, low sensitivity and resolution of older mass spectrometers, and popular peptide search engines being unable to handle more than a few PTMs at a time.
Recent advances in the MS-based proteomics field have led to the discovery of hundreds of new PTMs. Despite the dbPTM database containing over 70 types of PTMs, 3 of these (phosphorylation, acetylation, and ubiquitination) make up for ~90% of the total PTMs currently reported. Whether the low number of sites reflects a lack of interest in the novel modifications, or their natural abundance is still unclear. However, several research groups have found correlations between these uncommon PTMs and diseases.
This Research Topic aims to collect articles highlighting advances in the study of the less common PTMs. We hope this research topic will provide a compass for new researchers orienting themselves in this promising field and an opportunity for established ones to share their results and insights.
The potential manuscripts we are interested in include, but are not limited to, Original Research, Methods, Perspective, and Review articles covering the following topics:
- Discovery of uncharacterized PTMs
- Computational methods for the detection and localization of PTMs, especially in an “open modification search” context
- Computational methods to predict the effect of rare PTMs on protein structure and activity
- Correlation between rare PTMs and disease
- Address the current limitations in PTMs analysis and propose innovative solutions and methodologies to overcome these challenges
John M Aletta is Co-Founder and Research Director of CH3 BioSystems
Keywords:
posttranslational modification, bioinformatics, proteomics, open modification search, mass spectrometry
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Proteins are the product of gene expression and allow cells to perform their functions: from structural proteins that control a cell's shape to kinases involved in signal transduction.
The process that leads from the genetic information encoded in the DNA to a protein comprises two steps, transcription and translation. Whereas transcriptional, post-transcriptional and translational regulation mainly affect the type and amount of proteins in the cell, a more subtle layer of control involves the modifications a protein can undergo after its synthesis. Protein Post-Translational Modifications (PTMs), the covalent addition or removal of chemical groups to or from the side chains of some amino acid residues, play a pivotal role in regulating the function, subcellular localization, or stability of a protein and are related to the development of several diseases (cancer, diabetes, neurodegenerative diseases).
Due to the inevitable impact of PTMs on protein mass, the utilization of Tandem Mass Spectrometry (MS/MS) has emerged as a popular strategy for their study. Mass spectrometers record the peptides' fragmentation spectra, which are fed to software called peptide search engines that compare them to theoretical spectra generated by simulating in silico the fragmentation process. One advantage of MS/MS is that it is unbiased and thus can theoretically detect any mass shift (PTM) present on a peptide. In practice, researchers face various limitations: the low abundance of several PTMs, low sensitivity and resolution of older mass spectrometers, and popular peptide search engines being unable to handle more than a few PTMs at a time.
Recent advances in the MS-based proteomics field have led to the discovery of hundreds of new PTMs. Despite the dbPTM database containing over 70 types of PTMs, 3 of these (phosphorylation, acetylation, and ubiquitination) make up for ~90% of the total PTMs currently reported. Whether the low number of sites reflects a lack of interest in the novel modifications, or their natural abundance is still unclear. However, several research groups have found correlations between these uncommon PTMs and diseases.
This Research Topic aims to collect articles highlighting advances in the study of the less common PTMs. We hope this research topic will provide a compass for new researchers orienting themselves in this promising field and an opportunity for established ones to share their results and insights.
The potential manuscripts we are interested in include, but are not limited to, Original Research, Methods, Perspective, and Review articles covering the following topics:
- Discovery of uncharacterized PTMs
- Computational methods for the detection and localization of PTMs, especially in an “open modification search” context
- Computational methods to predict the effect of rare PTMs on protein structure and activity
- Correlation between rare PTMs and disease
- Address the current limitations in PTMs analysis and propose innovative solutions and methodologies to overcome these challenges
John M Aletta is Co-Founder and Research Director of CH3 BioSystems
Keywords:
posttranslational modification, bioinformatics, proteomics, open modification search, mass spectrometry
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.