Post Translational Modification

Post-translational modifications (PTMs) are key mechanisms for regulating protein function and represent a major focus in biological research. Creative Diagnostics offers comprehensive PTM analysis products and services to help you unlock the secrets of protein function.

What is PTM?

PTM refers to a series of chemical modification processes that occur after a protein is synthesized by the ribosome. During this process, specific enzymes catalyze the covalent attachment of chemical groups—often derived from small molecule metabolites—to the amino acid side chains of the protein, or modifications at the protein's N- or C-terminus. The core principle of PTM is the fine-tuning of protein function through the addition or removal of specific functional groups, based on the existing primary structure of the protein. These modifications are reversible covalent changes, meaning proteins can dynamically gain or lose specific chemical groups according to the cell's needs, thereby altering their biological properties. This reversibility allows cells to rapidly adjust protein function, enabling real-time responses to external stimuli.

Common post-translation modificationsFigure 1. An overview of the most common post-translational modifications in bacteria, showing the amino acid side chains which are most frequently modified.
(Source: Forrest S, et al. 2020)

More than 600 types of PTMs have been discovered in mammalian cells, involving various amino acid residues. Notably, certain key proteins (such as the p53 tumor suppressor protein) can be subject to up to 50 different PTMs simultaneously, and different combinations of these modifications can lead to entirely different functional states for the protein. PTM is not a simple, single modification process. A single protein often undergoes several different types of modifications at multiple amino acid sites. This combinatorial effect allows for extremely precise and diverse regulation of protein function, serving as a crucial mechanism for cells to adapt to environmental changes. Different modification states of the same protein can produce several, or even dozens, of distinct functional phenotypes—a phenomenon known as the existence of "protein isoforms."

Why is PTM so Important?

Post-translational modifications are key determinants of a protein's true functional role. PTMs drive cellular signaling, participate in epigenetic regulation, and influence protein interactions and recognition by altering a protein's physicochemical properties, three-dimensional structure, and biological activity. This makes them a vital mechanism for cells to rapidly adapt to environmental changes. Abnormal PTM patterns are closely linked to various diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases, making them important targets for disease diagnosis and therapy. Consequently, PTM is often hailed as the "goldmine of biological research"—merely knowing whether a protein is expressed is insufficient; it is essential to understand its modification state to fully grasp its actual function. Research into PTM holds core value for deeply understanding cell biology, disease mechanisms, and drug action.

Major Types of Protein Post-Translational Modifications

Modification Type Modification Mechanism Primary Functions Application
Phosphorylation Catalyzed by protein kinases; transfers a phosphate group to serine, threonine, or tyrosine residues. Activates or inhibits enzyme activity; participates in cellular signal transduction, metabolic regulation, and DNA damage repair; reversible. Cancer research, signal pathway analysis, kinase target development.
Glycosylation N-linked and O-linked forms; catalyzed by glycosyltransferases. Affects protein antigenicity, immunogenicity, biological activity, and in vivo metabolism. Biopharmaceuticals, protein drug quality control, vaccine development.
Ubiquitination A three-enzyme (E1-E2-E3) cascade attaches ubiquitin molecules to target proteins. Mediates 80%-85% of protein degradation in eukaryotes; regulates cell cycle and signaling. Cell cycle research, protein stability assessment, neurodegenerative disease research.
Acetylation A reversible modification acting on lysine residues. Affects nuclear histones and transcription factors; regulates cell cycle and metabolic management. Epigenetics research, metabolic disease studies, new drug target development.
Methylation Addition of methyl groups to proteins. Alters protein function and subcellular localization; involved in long-term gene expression regulation. Epigenetics, developmental biology, cancer research.

Other Emerging Modifications: With ongoing research, many new types are being discovered, including succinylation, hydroxybutyrylation, and lactylation. These new modifications show broad application prospects in metabolic regulation and disease prevention/therapy.

Application

  • In basic research, PTM analysis helps researchers understand the mechanisms of protein functional regulation, uncover cellular signaling pathways, and provide new perspectives for studying disease mechanisms.
  • In the biopharmaceutical field, the PTM status of protein therapeutics (such as monoclonal antibodies) directly impacts their stability, efficacy, and pharmacokinetic properties, making it a Critical Quality Attribute (CQA) for determining the quality and safety of biologic drugs.
  • In precision medicine, PTMomics holds significant promise for diagnostic and therapeutic applications across various fields, including cardiovascular diseases, neurodegenerative disorders, and infectious diseases.

Reference

  1. Forrest S, et al. Arming the troops: Post-translational modification of extracellular bacterial proteins. Sci Prog. 2020 Oct-Dec;103(4):36850420964317.
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