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Review
. 2021 Jan 21;9(1):2.
doi: 10.3390/proteomes9010002.

Misincorporation Proteomics Technologies: A Review

Joel R Steele  1   2 , Carly J Italiano  2 , Connor R Phillips  2 , Jake P Violi  1   2 , Lisa Pu  2 , Kenneth J Rodgers  2 , Matthew P Padula  1
Affiliations
Review

Misincorporation Proteomics Technologies: A Review

Joel R Steele et al. Proteomes. .

Erratum in

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.

Keywords: misincorporation; non protein amino acids; post translational modifications.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The transfer of amino acids (AA) onto tRNA through tRNA synthetase (aaRS) in the presence of ATP. ATP is converted to AMP activating the aaRS with the AA, an tRNA is then bound to the AA of the AA/aaRS/AMP complex subsequently the now charged tRNA dissociates.
Figure 2
Figure 2
Checks of mistranslation within a cell. AAs are checked for correct charging pre- and/or post-transfer. Misfolded species can be refolded via chaperones or degraded by the various proteolytic pathways; aggregates that are not degraded can lead to cell death.
Figure 3
Figure 3
How to compare mistranslated sequence abundances. Within a “Control” vs. “Treated” sample it is only possible to estimate the relative amount of the modified peptide species by a concurrent decrease in the amount of the unmodified peptide. This in essence is a decrease in the proteoform-typic peptide in comparison to the native proteoform-peptides.
See this image and copyright information in PMC

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