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M03.04.07 Co- and Post-Translational Covalent Modifications
Covalent modifications play a crucial role in determining the final structure and function of proteins. These modifications occur both during protein folding and after the protein has been fully synthesized. In addition to disulfide bond formation during the folding process, other key covalent modifications include glycosylation, proteolysis, phosphorylation, γ-carboxylation, and prenylation.
Types of Co- and Post-Translational Covalent Modifications
1. Glycosylation
- Definition: The addition of oligosaccharide chains to proteins.
- Location: This process occurs as proteins pass through the endoplasmic reticulum (ER) and the Golgi apparatus.
- Function: It plays a key role in protein stability, cell-cell recognition, and immune response.
2. Proteolysis
- Definition: The cleavage of peptide bonds within a protein.
- Examples: Proinsulin, trypsinogen, and prothrombin are all precursors that require cleavage to become active.
- Function: Proteolysis is essential for remodeling proteins and activating precursor molecules (zymogens).
3. Phosphorylation
- Definition: The addition of phosphate groups to specific amino acids in a protein.
- Enzyme: Protein kinases mediate this process.
- Function: Phosphorylation serves as a regulatory mechanism, influencing various cellular processes such as cell cycle progression, apoptosis, and signal transduction.
4. γ-Carboxylation
- Definition: The addition of carboxyl groups to certain glutamate residues.
- Function: This modification creates calcium (Ca²⁺) binding sites, which are important for blood coagulation factors.
5. Prenylation
- Definition: The attachment of hydrophobic farnesyl or geranylgeranyl lipid groups to specific proteins.
- Function: Prenylation targets proteins to membranes and is critical for their localization and function in cellular signaling pathways.
Table of Co- and Post-Translational Covalent Modifications
| Modification | Enzyme/Process | Function | Examples |
|---|---|---|---|
| Glycosylation | ER and Golgi enzymes | Stability, immune response | Glycoproteins |
| Proteolysis | Proteases | Activation of zymogens, protein remodeling | Proinsulin, trypsinogen |
| Phosphorylation | Protein kinases | Regulation of cellular processes | Cyclins, growth factor receptors |
| γ-Carboxylation | γ-Carboxylase | Calcium binding, blood clotting | Coagulation factors |
| Prenylation | Farnesyl transferase | Membrane targeting, signaling | RAS proteins |
Points to Remember
- Covalent modifications are critical for protein functionality.
- Glycosylation occurs in the ER and Golgi and aids in protein stability and recognition.
- Proteolysis is necessary for the activation of precursor proteins like proinsulin.
- Phosphorylation is a dynamic and reversible regulatory mechanism.
- γ-Carboxylation facilitates calcium binding, essential for blood coagulation.
- Prenylation helps in anchoring proteins to cell membranes for signaling functions.
Bibliography
- Lodish, H., Berk, A., & Zipursky, S. L. (2000). Molecular Cell Biology. New York: W. H. Freeman.
- Alberts, B., Johnson, A., Lewis, J., et al. (2015). Molecular Biology of the Cell. Garland Science.
- Berg, J. M., Tymoczko, J. L., & Stryer, L. (2015). Biochemistry. W.H. Freeman.