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Published on: May 4, 2022
Tools for analyzing and predicting N-terminal protein modifications
Thierry Meinnel1, Carmela Giglione
1Protein Maturation, Cell Fate and Therapeutics, Institut des Sciences du Végétal, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France. thierry.meinnel@isv.cnrs-gif.fr
Abstract:
The vast majority of the proteins encoded in any genome naturally undergo a large number of different N-terminal modifications, hindering their characterization by routine proteomic approaches. These modifications are often irreversible, usually cotranslational and are crucial, as their occurrence may reflect or affect the status, fate and function of the protein. For example, large signal peptide cleavages and N-blocking mechanisms reflect targeting to various cell compartments, whereas N-ligation events tend to be related to protein half-life. N-terminal positional proteomic strategies hold promise as a new generation of approaches to the fine analysis of such modifications. However, further biological investigation is required to resolve problems associated with particular low-abundance or challenging N-terminal modifications. Recent progress in genomics and bioinformatics has provided us with a means of assessing the impact of these modifications in proteomes. This review focuses on methods for characterizing the occurrence and diversity of N-terminal modifications and for assessing their contribution to function in complete proteomes. Progress is being made towards the annotation of databases containing information for complete proteomes, and should facilitate research into all areas of proteomics.
Insights
Most proteins undergo N-terminal modifications, impacting their function and cellular fate. New proteomic strategies are advancing the study of these crucial, yet challenging, protein modifications.
Area of Science:
- Proteomics
- Molecular Biology
- Genomics
Background:
- The majority of cellular proteins undergo N-terminal modifications, which are often cotranslational and irreversible.
- These modifications critically influence protein status, cellular localization, and function, affecting protein half-life and targeting.
- Routine proteomic methods face challenges in characterizing the diversity and impact of these N-terminal events.
Purpose of the Study:
- To review methods for characterizing N-terminal protein modifications.
- To assess the contribution of these modifications to protein function within complete proteomes.
- To highlight advancements in genomics and bioinformatics for studying N-terminal modifications.
Main Methods:
- Review of N-terminal positional proteomic strategies.
- Analysis of recent progress in genomics and bioinformatics.
- Focus on methods for characterizing occurrence, diversity, and functional impact.
Main Results:
- N-terminal modifications are crucial for protein fate and function, influencing cellular targeting and protein half-life.
- N-terminal positional proteomics offers a new generation of analytical approaches.
- Genomic and bioinformatics advancements aid in assessing the impact of these modifications on proteomes.
Conclusions:
- Further biological investigation is needed for low-abundance or challenging N-terminal modifications.
- Progress in database annotation is facilitating research across proteomics.
- Characterizing N-terminal modifications is essential for a comprehensive understanding of proteomes.
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