Proteoforms expand the world of microproteins and short open reading frame-encoded peptides

Cassidy, Liam; Kaulich, Philipp T.; Tholey, Andreas

doi:10.1016/j.isci.2023.106069

Cited by 11 publications

(10 citation statements)

References 86 publications

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“…In recent years, MS has become important, not only because of its ability to identify proteins (whether small or large), but also for its power to quantify and molecularly characterize them via the identification of posttranslational modifications. 78 , 81 …”

Section: Mass Spectrometry-based Proteomicsmentioning

confidence: 99%

No country for old methods: New tools for studying microproteins

Valdivia-Francia,

Sendoel

2024

iScience

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Section: Mass Spectrometry-based Proteomicsmentioning

confidence: 99%

No country for old methods: New tools for studying microproteins

Valdivia-Francia,

Sendoel

2024

iScience

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“…41 Proteogenomics can identify and characterize the structure of new coding sequences to better define their function through short open reading frames and their possible PTMs. 42 New methodologies may improve the functional characterization of protein−protein interactomes. 43 Overall, iMOP aims to federate expertise to improve structural and functional knowledge of proteins to answer fundamental biological questions using the most relevant biological model.…”

Section: Initiative For Model Organism Proteomics (Imop)mentioning

confidence: 99%

“…Proteomics has also identified a circadian clock in cyanobacteria, a key biological mechanism in new prokaryotic models . Proteogenomics can identify and characterize the structure of new coding sequences to better define their function through short open reading frames and their possible PTMs . New methodologies may improve the functional characterization of protein–protein interactomes .…”

Section: Biology and Disease-driven Hppmentioning

confidence: 99%

The 2023 Report on the Proteome from the HUPO Human Proteome Project

Omenn,

Lane,

Overall

et al. 2024

J. Proteome Res.

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Since 2010, the Human Proteome Project (HPP), the flagship initiative of the Human Proteome Organization (HUPO), has pursued two goals: (1) to credibly identify the protein parts list and (2) to make proteomics an integral part of multiomics studies of human health and disease. The HPP relies on international collaboration, data sharing, standardized reanalysis of MS data sets by PeptideAtlas and MassIVE-KB using HPP Guidelines for quality assurance, integration and curation of MS and non-MS protein data by neXtProt, plus extensive use of antibody profiling carried out by the Human Protein Atlas. According to the neXtProt release 2023-04-18, protein expression has now been credibly detected (PE1) for 18,397 of the 19,778 neXtProt predicted proteins coded in the human genome (93%). Of these PE1 proteins, 17,453 were detected with mass spectrometry (MS) in accordance with HPP Guidelines and 944 by a variety of non-MS methods. The number of neXtProt PE2, PE3, and PE4 missing proteins now stands at 1381. Achieving the unambiguous identification of 93% of predicted proteins encoded from across all chromosomes represents remarkable experimental progress on the Human Proteome parts list. Meanwhile, there are several categories of predicted proteins that have proved resistant to detection regardless of protein-based methods used. Additionally there are some PE1–4 proteins that probably should be reclassified to PE5, specifically 21 LINC entries and ∼30 HERV entries; these are being addressed in the present year. Applying proteomics in a wide array of biological and clinical studies ensures integration with other omics platforms as reported by the Biology and Disease-driven HPP teams and the antibody and pathology resource pillars. Current progress has positioned the HPP to transition to its Grand Challenge Project focused on determining the primary function(s) of every protein itself and in networks and pathways within the context of human health and disease.

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“…This technology has particular importance for identification of microprotein proteoforms, a term that refers to all post-transcriptionally and/or post-translationally processed protein products arising from a single gene [107,108]. For example, microproteins and other noncanonical proteins can exhibit multiple proteoforms as a result of alternative splicing [109], Nterminal proteolytic processing [110], phosphorylation [111,112], and other post-translational modifications [107], and most of this variability is obscured in bottom-up proteomic analyses as a result of incomplete sequence coverage and inability to distinguish whether modifications on different tryptic fragments occur on the same, or mutually exclusive, proteoforms [107]. Top-down analysis has identified novel microprotein proteoforms in microorganisms [80], and its expanded adoption should accelerate the identification of microprotein N-and C-termini as well as functional modification states in the future.…”

Section: Mass Spectrometrymentioning

confidence: 99%

Microproteins—Discovery, structure, and function

Mohsen,

Martel,

Slavoff

2023

Proteomics

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Advances in proteogenomic technologies have revealed hundreds to thousands of translated small open reading frames (sORFs) that encode microproteins in genomes across evolutionary space. While many microproteins have now been shown to play critical roles in biology and human disease, a majority of recently identified microproteins have little or no experimental evidence regarding their functionality. Computational tools have some limitations for analysis of short, poorly conserved microprotein sequences, so additional approaches are needed to determine the role of each member of this recently discovered polypeptide class. A currently underexplored avenue in the study of microproteins is structure prediction and determination, which delivers a depth of functional information. In this review, we provide a brief overview of microprotein discovery methods, then examine examples of microprotein structures (and, conversely, intrinsic disorder) that have been experimentally determined using crystallography, cryo‐electron microscopy, and NMR, which provide insight into their molecular functions and mechanisms. Additionally, we discuss examples of predicted microprotein structures that have provided insight or context regarding their function. Analysis of microprotein structure at the angstrom level, and confirmation of predicted structures, therefore, has potential to identify translated microproteins that are of biological importance and to provide molecular mechanism for their in vivo roles.

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Proteoforms expand the world of microproteins and short open reading frame-encoded peptides

Cited by 11 publications

References 86 publications

No country for old methods: New tools for studying microproteins

No country for old methods: New tools for studying microproteins

The 2023 Report on the Proteome from the HUPO Human Proteome Project

Microproteins—Discovery, structure, and function

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