Histone Modifications in Neurological Disorders

Smith, Bradley J.; Carregari, Victor Corasolla

doi:10.1007/978-3-031-05460-0_7

Cited by 5 publications

(3 citation statements)

References 88 publications

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“…PTMs play such an important role for histone proteins that they presumably constitute an epigenetic code (the "histone code" hypothesis) [7]. PTMs regulate the genome during cell fate determination and development and are implicated in disease-related cellular processes, including cancers, neurological disorders or autoimmune diseases [8,9]. With more than 400 known PTMs to date and enzymes responsible for over 200 types of modifications of protein substrates [10,11], the vast number of potential PTM combinations along with the reversible nature of many of them, gives rise to an abundant number of proteoforms.…”

Section: Introductionmentioning

confidence: 99%

Top‐down ion mobility/mass spectrometry reveals enzyme specificity: Separation and sequencing of isomeric proteoforms

Berthias,

Bilgin,

Mecinović

et al. 2024

Proteomics

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Enzymatic catalysis is one of the fundamental processes that drives the dynamic landscape of post‐translational modifications (PTMs), expanding the structural and functional diversity of proteins. Here, we assessed enzyme specificity using a top‐down ion mobility spectrometry (IMS) and tandem mass spectrometry (MS/MS) workflow. We successfully applied trapped IMS (TIMS) to investigate site‐specific N‐ε‐acetylation of lysine residues of full‐length histone H4 catalyzed by histone lysine acetyltransferase KAT8. We demonstrate that KAT8 exhibits a preference for N‐ε‐acetylation of residue K16, while also adding acetyl groups on residues K5 and K8 as the first degree of acetylation. Achieving TIMS resolving power values of up to 300, we fully separated mono‐acetylated regioisomers (H4K5ac, H4K8ac, and H4K16ac). Each of these separated regioisomers produce unique MS/MS fragment ions, enabling estimation of their individual mobility distributions and the exact localization of the N‐ε‐acetylation sites. This study highlights the potential of top‐down TIMS‐MS/MS for conducting enzymatic assays at the intact protein level and, more generally, for separation and identification of intact isomeric proteoforms and precise PTM localization.

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Section: Introductionmentioning

confidence: 99%

Top‐down ion mobility/mass spectrometry reveals enzyme specificity: Separation and sequencing of isomeric proteoforms

Berthias,

Bilgin,

Mecinović

et al. 2024

Proteomics

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“…Post-translational modification (PTM) of proteins diversify proteome function by covalently adding small proteins or other groups, potentially altering their cellular localization, interaction with partners, and activation state ( Schweppe et al, 2003 ; Zolg et al, 2018 ). The disruption of PTMs can upset normal physiological processes ( Gupta et al, 2021 ; He et al, 2021 ; Smith and Carregari, 2022 ). The rapid development of proteomics and mass spectrometry has identified an increasing number of PTMs, including glycosylation, ubiquitination, methylation, phosphorylation, acetylation, and lipidation ( Aslebagh et al, 2019 ; Andres et al, 2020 ; Hermann et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Role of protein Post-translational modifications in enterovirus infection

Zhao,

Hu,

Zhao

et al. 2024

Front. Microbiol.

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Enteroviruses (EVs) are the main cause of a number of neurological diseases. Growing evidence has revealed that successful infection with enteroviruses is highly dependent on the host machinery, therefore, host proteins play a pivotal role in viral infections. Both host and viral proteins can undergo post-translational modification (PTM) which can regulate protein activity, stability, solubility and interactions with other proteins; thereby influencing various biological processes, including cell metabolism, metabolic, signaling pathways, cell death, and cancer development. During viral infection, both host and viral proteins regulate the viral life cycle through various PTMs and different mechanisms, including the regulation of host cell entry, viral protein synthesis, genome replication, and the antiviral immune response. Therefore, protein PTMs play important roles in EV infections. Here, we review the role of various host- and virus-associated PTMs during enterovirus infection.

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“…PTMs play such an important role for histone proteins that they presumably constitute an epigenetic code (the "histone code" hypothesis) [7]. PTMs regulate the genome during cell fate determination and development and are implicated in disease-related cellular processes, including cancers, neurological disorders or autoimmune diseases [8,9]. With more than 400 known PTMs to date and enzymes responsible for over 200 kinds of modifications of protein substrates [10,11], the vast number of potential PTM combinations along with the reversible nature of many of them, gives rise to an abundant number of proteoforms.…”

Section: Introductionmentioning

confidence: 99%

Top-down ion mobility/mass spectrometry reveals enzyme specificity: Separation and sequencing of isomeric proteoforms

Berthias

Bilgin

Mecinović

et al. 2023

Preprint

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Enzymatic catalysis is one of the fundamental processes that drives the dynamic landscape of post-translational modifications (PTMs), expanding the structural and functional diversity of proteins. Here, we assessed enzyme specificity using a top-down ion mobility spectrometry (IMS) and tandem mass spectrometry (MS/MS) workflow. We successfully applied trapped IMS (TIMS) to investigate site-specific N-ε-acetylation of lysine residues of full-length histone H4 catalyzed by histone lysine acetyltransferase KAT8. We demonstrate that KAT8 exhibits a preference for N-ε-actylation of residue K16, while also installing N-ε-acetyl groups on residues K5 and K8 as the first degree of acetylation. Achieving TIMS resolving power values of up to 300, we fully separated mono-acetylated regioisomers (H4K5ac, H4K8ac, and H4K16ac). Each of these regioisomers produce unique MS/MS fragment ions, enabling estimation of their individual mobility distributions and the exact localization of the N-ε-acetylation sites. This study highlights the potential of top-down TIMS-MS/MS for conducting enzymatic assays at the intact protein level and, more generally, for separation and identification of isomeric proteoforms and precise PTM localization.

show abstract

Histone Modifications in Neurological Disorders

Cited by 5 publications

References 88 publications

Top‐down ion mobility/mass spectrometry reveals enzyme specificity: Separation and sequencing of isomeric proteoforms

Top‐down ion mobility/mass spectrometry reveals enzyme specificity: Separation and sequencing of isomeric proteoforms

Role of protein Post-translational modifications in enterovirus infection

Top-down ion mobility/mass spectrometry reveals enzyme specificity: Separation and sequencing of isomeric proteoforms

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