Why Is Lysine Acylation Considered a Key Post-Translational Modification (PTM)?
- Neutralizing the positive charge of lysine residues: This affects protein structural stability, spatial conformation, and interactions with DNA, RNA, or other proteins.
- Modifying protein conformation and functional activity: For example, histone acetylation facilitates chromatin relaxation and promotes transcriptional activation; acylation of non-histone proteins frequently modulates enzymatic activity or signaling processes.
- Propionylation
- Butyrylation
- Valerylation
- Succinylation
- Malonylation
- As well as glutarylation, formylation, hydroxybutyrylation, and others
- Efficient enrichment protocols for acylated peptides
- High-accuracy identification based on Orbitrap high-resolution mass spectrometry
- Quantitative profiling of multiple newly characterized acylation markers
- Computational data mining and functional pathway enrichment analysis
Lysine acylation represents a class of post-translational modifications (PTMs) occurring on lysine residues and encompasses the canonical acetylation as well as multiple newly characterized acylation types (including propionylation, butyrylation, valerylation, malonylation, succinylation, and others). In recent years, the advancement of high-resolution mass spectrometry has enabled broad detection and characterization of these modifications and has established lysine acylation as an important molecular mechanism underlying the regulation of cellular physiology.
Key Mechanism Regulating Protein Function
Lysine acylation can profoundly alter the physicochemical properties of proteins by:
Accordingly, lysine acylation functions not only as a structural modification but also as a dynamic molecular switch regulating protein function.
Broad Participation in Multiple Cellular Processes
Proteins carrying lysine acylation modifications are distributed across diverse subcellular compartments, including the nucleus, mitochondria, cytoplasm, and plasma membrane, and contribute to the regulation of a wide range of biological processes, including but not limited to:
1. Epigenetic Regulation
Histone lysine acetylation was among the earliest identified acylation types and directly influences chromatin accessibility and transcriptional output.
2. Energy Metabolism Regulation
Numerous mitochondrial metabolic enzymes exhibit lysine acylation, affecting processes such as the tricarboxylic acid cycle, fatty acid oxidation, and oxidative phosphorylation.
3. Cell Cycle and Proliferation
Certain acylation modifications are associated with the activation and degradation of cell cycle-related proteins.
4. Signal Transduction
Lysine acylation has been identified on key signaling regulators, including p53 and NF-κB.
5. Immune and Stress Responses
This includes regulation of inflammatory cytokine production and oxidative stress responses.
Closely Associated With Diseases
Aberrant lysine acylation states are implicated in the onset and progression of multiple diseases, particularly:
1. Cancer
(1) Dysregulated acylation of both histone and non-histone proteins is frequently observed in tumor cells.
(2) Specific histone acetyltransferases (HATs) and deacetylases (HDACs) have been shown to possess oncogenic properties.
(3) Novel acylation types (e.g., succinylation) are closely linked to metabolic reprogramming in cancer.
2. Neurological Diseases
(1) In Alzheimer’s disease (AD), aberrant acylation of proteins such as Tau and α-synuclein has been reported.
(2) Acylation modulates mitochondrial function, thereby influencing neuronal energy metabolism and survival.
3. Metabolic Diseases
In metabolic disorders including diabetes, obesity, and fatty liver disease, lysine acylation participates in the regulation of insulin signaling pathways and lipid metabolism.
Newly Identified Acylation Forms Reveal Richer Regulatory Networks
With improvements in mass spectrometry technologies, increasing numbers of lysine acylation types continue to be identified, including:
Most of these newly characterized modifications derive from metabolic intermediates, illustrating a direct connection between metabolic states and epigenetic regulation and comprising the so-called metabolism-epigenetic regulatory axis.
Mass Spectrometry Drives Research Into the Systems Biology Stage
Recently, high-resolution mass spectrometry platforms (such as Orbitrap Exploris and timsTOF), combined with acylation enrichment strategies (including antibody-based enrichment and chemical labeling), have markedly improved the detectability and characterization of acylation events.
At MtoZ Biolabs, we provide a one-stop lysine acylation proteomics workflow, including:
We aim to enable researchers to dissect acylation regulatory networks from a systems-level perspective and to support mechanistic investigations and disease-related target discovery.
Lysine acylation, one of the most diverse and functionally versatile classes of post-translational protein modifications, is transitioning from descriptive profiling toward mechanistic interrogation and potential clinical translation. Across areas such as epigenetic regulation, metabolic control, and biomarker discovery, it demonstrates substantial promise. As novel modification types continue to be discovered and the corresponding modifying enzymes are elucidated, research on lysine acylation is expected to gain further momentum in life sciences. For researchers working in this area, MtoZ Biolabs offers high-quality acylation proteomics services to accelerate scientific discovery.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
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