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Published on: November 15, 2017
Misincorporation Proteomics Technologies: A Review
Joel R Steele1,2, Carly J Italiano2, Connor R Phillips2
1Proteomics Core Facility and School of Life Sciences, The University of Technology Sydney, Ultimo, NSW 2007, Australia.
Abstract:
Proteinopathies are diseases caused by factors that affect proteoform conformation. As such, a prevalent hypothesis is that the misincorporation of noncanonical amino acids into a proteoform results in detrimental structures. However, this hypothesis is missing proteomic evidence, specifically the detection of a noncanonical amino acid in a peptide sequence. This review aims to outline the current state of technology that can be used to investigate mistranslations and misincorporations whilst framing the pursuit as Misincorporation Proteomics (MiP). The current availability of technologies explored herein is mass spectrometry, sample enrichment/preparation, data analysis techniques, and the hyphenation of approaches. While many of these technologies show potential, our review reveals a need for further development and refinement of approaches is still required.
Insights
Detecting noncanonical amino acids in proteins is crucial for understanding diseases like proteinopathies. This review explores current technologies for Misincorporation Proteomics (MiP), highlighting the need for further advancements in this field.
Area of Science:
- Biochemistry and Molecular Biology
- Proteomics
- Disease Mechanisms
Background:
- Proteinopathies arise from altered proteoform structures.
- A key hypothesis suggests noncanonical amino acid misincorporation causes these detrimental structures.
- Proteomic evidence for this hypothesis, specifically detecting noncanonical amino acids in peptides, is currently lacking.
Purpose of the Study:
- To review existing technologies for investigating protein mistranslations and misincorporations.
- To establish the framework for Misincorporation Proteomics (MiP).
- To identify technological gaps and areas for future development in MiP.
Main Methods:
- Review of current mass spectrometry techniques.
- Assessment of sample enrichment and preparation strategies.
- Evaluation of data analysis approaches and hyphenated techniques.
Main Results:
- Current technologies, including mass spectrometry and advanced data analysis, show potential for detecting misincorporated amino acids.
- The integration of various approaches (hyphenation) is a promising strategy.
- Significant limitations and a need for refinement exist across all explored technological domains.
Conclusions:
- Despite technological advancements, direct proteomic evidence for noncanonical amino acid misincorporation remains challenging to obtain.
- Further development and optimization of mass spectrometry, sample handling, and data interpretation are essential for advancing Misincorporation Proteomics.
- Establishing robust MiP methodologies is critical for validating hypotheses about proteinopathies and related diseases.
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