Post-Translational Modifications, PTMs
Once a peptide or protein is synthesized, it often undergoes post-translational modifications, PTMs that regulate its activity, stability, and interactions with other molecules. PTMs are essential for fine-tuning protein function and expanding the diversity of peptide activities within cells. Common modifications include phosphorylation, glycosylation, acetylation, and ubiquitination, each of which plays a distinct role in cellular processes.
Phosphorylation
Phosphorylation is one of the most studied PTMs, involving the addition of a phosphate group to specific amino acid residues, usually serine, threonine, or tyrosine. This modification is catalyzed by kinases and reversed by phosphatases. Phosphorylation plays a critical role in cell signaling pathways, particularly in the regulation of enzyme activity, protein-protein interactions, and gene expression.1 For example, phosphorylation of the tumor suppressor p53 activates its role in DNA damage response and apoptosis.
Glycosylation
Glycosylation involves the attachment of carbohydrate groups to asparagine, serine, or threonine residues on proteins. This PTM is critical for protein folding, stability, and recognition by the immune system. Glycosylated proteins, such as antibodies and hormones, rely on this modification for their proper function. In particular, the glycosylation of immunoglobulins influences their ability to bind to immune cells and activate immune responses.2
Other Modifications
Other important PTMs include acetylation, which often occurs on lysine residues and regulates chromatin structure and gene expression, and ubiquitination, which tags proteins for degradation by the proteasome. Additionally, disulfide bond formation between cysteine residues stabilizes the tertiary and quaternary structures of extracellular proteins such as insulin and immunoglobulins.3
Conclusion
Post-translational modifications are vital for regulating protein function and ensuring cellular homeostasis. Phosphorylation, glycosylation, acetylation, and other modifications provide mechanisms for dynamic control of protein activity, enabling cells to respond rapidly to environmental and physiological changes. Understanding these modifications is crucial for developing therapeutic strategies targeting specific proteins and pathways.
Citations and Links
1. Hunter, Tony. “Protein Phosphorylation: The Story of a Paradigm.” Journal of Cell Biology, vol. 168, no. 2, 2005, pp. 203-213. doi:10.1083/jcb.200409073.
2. Apweiler, Rolf, et al. “On the Frequency of Protein Glycosylation, as Deduced from Analysis of the SWISS-PROT Database.” Bioinformatics, vol. 15, no. 10, 1999, pp. 810-824.
3. Creighton, Thomas E. Proteins: Structures and Molecular Properties. W. H. Freeman, 1993.
Illustrations