Post Translational Modifications

Translation in biology is a process in which a molecule of messenger RNA is sequenced to amino acid during protein synthesis.

Post-translational modifications refer to the changes occurring to the protein with the help of enzymes after protein synthesis.

Definition 

Post-translational modifications involve modifications of the amino acid chain, terminal amino, or carboxyl group by enzymes. Due to these modifications, the structure, stability, or activity of the proteins get affected. The processes which cause modifications are phosphorylation, methylation, glycosylation, nitrosylation, ubiquitination, acetylation, lipidation, and proteolysis.

Post-translational modifications in proteins

In Post-translational modifications, the polypeptide chains are synthesized by going through translation inside the cell cytoplasm. These polypeptides are immediately used for different functional activities or covalent modifications of functional groups. 

Types of post-translational modifications

• Glycosylation 

Protein glycosylation is one of the complex forms of post-translational modifications and is formed by the addition of carbohydrate molecules to an amino acid to form a glycoprotein. Glycosylation is further divided into two types- N-linked glycosylation, where, a sugar molecule is attached to the amide nitrogen of asparagine, and O-linked glycosylation, where, sugar molecules are attached to the oxygen atom of serine or threonine. 

• Phosphorylation 

It occurs in the reversible attachment of the phosphate group to a specific residue of the target protein. Phosphorylation is catalyzed by protein kinases and phosphatases. Phosphorylation is important for cell growth, cell cycle, and signal transduction pathways. Protein phosphorylation is the most studied post-translational modification and can be used in disease processes such as cancer.

• Ubiquitination 

Ubiquitination regulates many processes such as cell cycle, cell growth, functions of the immune system, membrane exchange, DNA restoration, transcription. Ubiquitination is catalyzed by many enzymes – in the first step, Ubiquitin activating enzyme, a catalytic cysteine, and a carboxyl group for a thioester bond. In the second step, the ubiquitin molecule is transferred to an E2 ubiquitin transferring enzyme. 

Monoubiquitination means the addition of one ubiquitin molecule and Polyubiquitination means the addition of several ubiquitin molecules. 

• Proteolysis

This process includes limited and highly hydrolyzed peptide and isopeptide bonds protease, ubiquitous and thermodynamically favorable, and irreversible modification. Proteolysis is a regulator mechanism and its activity can be controlled by proteolytic induction. Proteolysis is a thermodynamically favorable and irreversible reaction. Proteases are broadly divided into four categories- serine proteases, cysteine proteases, aspartic acid proteases, Zinc metalloproteases.

• Protein methylation 

Protein methylation is quite important in processes such as gene transcription and signal transduction.  In protein methylation, the methyltransferases enzyme adds a methyl group to the specific amino acid on a protein molecule like lysine and arginine residues. Protein methylation is effective for protein stability, subcellular localization, binding affinity, and protein-protein interactions. 

• Acetylation 

Most common in eukaryotes, acetylation consists of addition of acetyl group to nitrogen through reversible or irreversible processes. When acetylation was studied in histones, it was observed that acetylation of the lysine side chain on the N-terminus of histones regulates gene expression. If lysine is acetylated, the binding of DNA to histone is relaxed leading to gene transcription

• Lipidation

By lipidation, proteins are targeted to membranes in organelles, such as Golgi Apparatus,  mitochondria, vesicles, and plasma membranes. There are four types of lipidation- c-terminal glycosylphosphatidylinositol (GPI) anchor, N-terminal myristoylation, S- myristoylation, S- prenylation.

GPI anchors which are made in the endoplasmic reticulum, are added to the new protein block. GPI anchored proteins are localized to cholesterol and sphingolipid-rich lipid rafts that act as signaling platforms on the plasma membrane.  

N-myristoylation gives proteins a hydrophobic handle for membrane localization and is catalyzed by N- myristoyl transferase and uses myristoyl- coenzyme A as a substrate to attach the myristoyl group to N-terminal glycine.

Conclusion

Post-translational modification of proteins plays some significant functions in cell growth, cell processes, etc. The post-translational modifications of proteins are important for controlling the stability of protein, localization, and conformation. By multiple post-translational modifications, genetic information imbibed in DNA is transcribed, translated, and increases its complexity. 

Post-translational modifications help in the mediation of stress perception, protein homeostasis, energy shift control, and defense by the immune system.