Post-Translational Modifications in prokaryotes and eukaryotes - Types, Functions, and Examples

Summary

This video provides a clear and comprehensive overview of post-translational modifications (PTMs), essential chemical changes that occur to proteins after translation. It explains how PTMs, including phosphorylation, methylation, acetylation, glycosylation, ubiquitination, sumoylation, proteolysis, and protein splicing, regulate protein activity, stability, localization, and interactions, thereby increasing protein diversity. The video illustrates each modification with specific cellular examples, such as growth factor signaling, histone regulation, blood group determination, and insulin activation. It also highlights the clinical relevance of PTMs, showing how defects can lead to diseases like cancer, immune deficiencies, liver cirrhosis, and diabetes.

Takeaways

• 😀 Post-translational modifications (PTMs) are chemical changes to proteins after translation that can activate or deactivate protein functions.
• 😀 PTMs are critical for protein stability, activity, localization, and interaction with other biomolecules.
• 😀 A single gene can produce multiple mRNA variants through alternative splicing, and PTMs further increase protein diversity in cells.
• 😀 Major types of PTMs include phosphorylation, methylation, acetylation, glycosylation, ubiquitination, sumoylation, proteolysis, and protein splicing.
• 😀 Phosphorylation, mediated by kinases, is essential for signaling pathways, cell cycle regulation, and transcription factor activation.
• 😀 Methylation and acetylation of histones regulate chromatin structure and gene expression.
• 😀 Glycosylation adds sugar molecules to proteins, influencing folding, stability, and cellular distribution, with examples like blood group determination.
• 😀 Ubiquitination tags proteins for degradation via the proteasome, helping maintain protein turnover and quality control.
• 😀 Sumoylation modifies protein transport between cytoplasm and nucleus and regulates transcription and stress response.
• 😀 Proteolysis cleaves peptide bonds to activate precursor proteins, process antigens, or form functional hormones like insulin.
• 😀 Protein splicing, found mainly in bacteria and lower eukaryotes, removes internal protein segments to regulate activity and stress responses.
• 😀 Defects in PTMs are linked to various diseases, including cancer, immune deficiencies, liver cirrhosis, diabetes, and blood clotting disorders.

Q & A

What are post-translational modifications (PTMs)?

Post-translational modifications are chemical changes to proteins that occur after translation, which can be reversible or irreversible. They are mainly enzymatic and covalent, helping proteins achieve their mature, functional forms.

How do PTMs affect protein function?

PTMs can activate or deactivate proteins, regulate their stability, control their localization, influence interactions with other biomolecules, and increase protein diversity within a cell.

Why is protein diversity greater than the number of genes in a cell?

A single gene can produce multiple mRNAs via alternative splicing or alternative promoters. Each mRNA can then be modified post-translationally, generating multiple functional protein variants from the same gene.

What are the four major classes of PTMs?

1) Functional group addition (e.g., phosphorylation, acetylation, methylation), 2) Protein tag addition (e.g., ubiquitination, sumoylation), 3) Backbone cleavage (e.g., proteolysis, protein splicing), and 4) Amino acid modifications (e.g., oxidation, deamination).

How does phosphorylation regulate cellular processes?

Phosphorylation involves the addition of a phosphate group to proteins, usually by kinases. It regulates signaling pathways, cell cycle progression, growth, and transcription by altering protein activity and localization.

What roles do methylation and acetylation play in chromatin structure?

Methylation of histones increases DNA packaging, making it less accessible, whereas acetylation relaxes DNA packaging, making chromatin more open and accessible for transcription.

Can you give an example of glycosylation in human biology?

Glycosylation adds sugar molecules to proteins, affecting their folding, stability, and distribution. An example is glycoproteins on red blood cells, where specific sugar patterns determine ABO blood groups.

What is the function of ubiquitination in eukaryotic cells?

Ubiquitination tags proteins for degradation by the 26S proteasome. It helps remove misfolded proteins, maintains protein homeostasis, and regulates protein turnover.

How does sumoylation differ from ubiquitination?

Sumoylation adds a SUMO protein tag, which does not target proteins for degradation. Instead, it regulates protein transport between the nucleus and cytoplasm and modulates protein stability and activity.

What is proteolysis, and why is it important?

Proteolysis involves cleaving peptide bonds to activate proteins or release functional domains. Examples include insulin maturation and fibrin formation for blood clotting.

What is protein splicing and in which organisms is it commonly found?

Protein splicing removes internal amino acid sequences (inteins) from a protein, analogous to RNA splicing. It is mainly observed in bacteria and lower eukaryotes and is often involved in stress responses.

How can defects in PTMs contribute to disease?

Defective PTMs can cause diseases such as cancer (phosphorylation, methylation, acetylation defects), immune disorders (glycosylation defects), uncontrolled cell growth (ubiquitination defects), and blood clotting or diabetes issues (proteolysis defects).