Write a note on post translational modifications of protein.

Types of Post-Translational Modifications

PTMs can be broadly categorized into enzymatic and non-enzymatic modifications. Enzymatic modifications are catalyzed by specific enzymes, while non-enzymatic modifications occur spontaneously or through abiotic factors.

1. Enzymatic Modifications

• Phosphorylation: The addition of a phosphate group to serine, threonine, or tyrosine residues, catalyzed by kinases. It’s a reversible process regulated by phosphatases. Phosphorylation often acts as a molecular switch, altering protein activity. Example: Regulation of glycogen metabolism by glycogen phosphorylase kinase.
• Glycosylation: The attachment of carbohydrate moieties to proteins. It can be N-linked (to asparagine) or O-linked (to serine or threonine). Glycosylation influences protein folding, stability, and cell-cell recognition. Example: Antibodies are heavily glycosylated, affecting their effector functions.
• Ubiquitination: The attachment of ubiquitin, a small protein, to a target protein. It can signal for protein degradation (via the proteasome), alter protein localization, or regulate protein activity. Example: Degradation of misfolded proteins via the ubiquitin-proteasome system.
• Acetylation: The addition of an acetyl group, typically to lysine residues. It often regulates gene expression by altering chromatin structure. Example: Histone acetylation promotes gene transcription.
• Methylation: The addition of a methyl group, often to lysine or arginine residues. It can affect gene expression and protein-protein interactions. Example: DNA methylation is a key epigenetic mechanism.
• Lipidation: The attachment of lipid molecules, such as myristoylation or palmitoylation, to proteins. It often targets proteins to cell membranes. Example: Src kinase is myristoylated for membrane localization.
• Proteolytic Cleavage: The cleavage of a protein precursor into smaller, functional fragments. Example: Activation of proinsulin to insulin by proteolytic cleavage.

2. Non-Enzymatic Modifications

• Hydroxylation: The addition of a hydroxyl group, often to proline or lysine residues. It’s important for collagen stability.
• Disulfide Bond Formation: The formation of covalent bonds between cysteine residues, stabilizing protein structure.
• Deamidation: The conversion of asparagine or glutamine to aspartic or glutamic acid, respectively.

Functional Consequences of PTMs

PTMs have profound effects on protein function:

• Protein Folding and Stability: Glycosylation and disulfide bond formation contribute to proper protein folding and stability.
• Protein Localization: Lipidation and glycosylation can target proteins to specific cellular compartments.
• Protein Activity: Phosphorylation, acetylation, and ubiquitination can directly regulate protein activity.
• Protein-Protein Interactions: PTMs can create or disrupt binding sites for other proteins.
• Signal Transduction: Many signaling pathways rely on PTMs to transmit information.

Techniques for Studying PTMs

Several techniques are used to identify and characterize PTMs:

• Mass Spectrometry: A powerful technique for identifying and quantifying PTMs.
• Western Blotting: Used to detect specific PTMs using antibodies.
• Phosphoproteomics: Specifically focuses on identifying phosphorylated proteins.
• Glycomics: Studies the carbohydrate structures of glycoproteins.

Modification	Enzyme Involved	Functional Effect
Phosphorylation	Kinases & Phosphatases	Regulation of activity, signaling
Glycosylation	Glycosyltransferases	Folding, stability, cell recognition
Ubiquitination	E1, E2, E3 Ubiquitin Ligases	Protein degradation, signaling