Translation and Post-Translational Modifications


Introduction

Translation and post-translational modifications (PTMs) are two essential processes that play a critical role in the production and function of proteins in living cells. Translation is the process by which the genetic information encoded in the messenger RNA (mRNA) is converted into a functional protein.

PTMs are covalent modifications that occur after translation and affect the structure, activity, localization, and stability of proteins. In this article, we will discuss translation and post-translational modifications in detail, including the steps involved, types of PTMs, and their applications.

Translation

Translation is a complex process that occurs in the cytoplasm of eukaryotic cells and involves the ribosome, mRNA, and transfer RNA (tRNA).

The process of translation can be divided into three steps: initiation, elongation, and termination.

Initiation

Initiation is the first step of translation, in which the small ribosomal subunit binds to the mRNA, and the initiator tRNA carrying methionine (Met-tRNA) binds to the start codon AUG. The large ribosomal subunit then joins, forming a complete ribosome.

Elongation

Elongation is the second step of translation, in which the ribosome moves along the mRNA, synthesizing the polypeptide chain one amino acid at a time. Each amino acid is brought to the ribosome by a specific tRNA that recognizes the codon on the mRNA. The amino acids are then joined by peptide bonds to form a growing polypeptide chain.

Termination

Termination is the final step of translation, in which the ribosome reaches a stop codon on the mRNA, and the newly synthesized polypeptide chain is released from the ribosome. The ribosome then dissociates into its two subunits, and the newly synthesized protein folds into its three-dimensional structure.

Post-Translational Modifications

PTMs are chemical modifications that occur after translation and affect the function, stability, and localization of proteins. There are many types of PTMs, including phosphorylation, acetylation, glycosylation, ubiquitination, methylation, and others.

  • Phosphorylation: Phosphorylation is the addition of a phosphate group to a protein, usually on a serine, threonine, or tyrosine residue. This modification can affect the activity, stability, localization, and interaction of proteins.

  • Acetylation: Acetylation is the addition of an acetyl group to a lysine residue. This modification can affect the stability, activity, and interaction of proteins.

  • Glycosylation: Glycosylation is the addition of a carbohydrate molecule to a protein. This modification can affect the stability, activity, and localization of proteins.

  • Ubiquitination: Ubiquitination is the addition of an ubiquitin molecule to a lysine residue on a protein. This modification can target the protein for degradation by the proteasome or affect its activity and localization.

  • Methylation: Methylation is the addition of a methyl group to a protein, usually on a lysine or arginine residue. This modification can affect the activity, stability, and interaction of proteins.

Applications

PTMs play a crucial role in many biological processes, including signal transduction, gene expression, and cell cycle regulation. PTMs also play a significant role in the pathogenesis of many diseases, including cancer, neurodegenerative diseases, and metabolic disorders.

Cancer

PTMs have been shown to play a critical role in the development and progression of cancer. For example, phosphorylation of proteins in the RAS-RAF-MEK-ERK pathway can lead to uncontrolled cell proliferation and tumor growth.

Neurodegenerative Diseases

PTMs have also been implicated in the development of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In Alzheimer’s disease, the abnormal phosphorylation of tau protein leads to the formation of neurofibrillary tangles, a hallmark of the disease.

In Parkinson’s disease, the aggregation of alpha-synuclein protein is thought to be facilitated by PTMs such as phosphorylation and ubiquitination.

Drug Development

Understanding the role of PTMs in disease pathogenesis has led to the development of drugs that target specific PTMs. For example, drugs that inhibit protein kinases, enzymes that catalyze the phosphorylation of proteins, are used to treat cancer and inflammatory diseases.

Drugs that inhibit histone deacetylases, enzymes that remove acetyl groups from histones, are used to treat cancer and neurological disorders.

FAQs

Q1. What is translation?

Ans. Translation is the process by which the genetic information encoded in the messenger RNA (mRNA) is converted into a functional protein.

Q2. What is post-translational modification?

Ans. Post-translational modification (PTM) refers to the covalent modification of proteins after they have been synthesized by the ribosome during translation.

Q3. What are some common types of PTMs?

Ans. Some common types of PTMs include phosphorylation, acetylation, glycosylation, ubiquitination, and methylation.

Q4. How do PTMs affect protein function?

Ans. PTMs can affect protein function by altering protein activity, stability, localization, and interaction with other molecules.

Q5. What is the role of PTMs in disease?

Ans. PTMs have been implicated in the pathogenesis of many diseases, including cancer, neurodegenerative diseases, and metabolic disorders.

Q6. How are PTMs studied?

Ans. PTMs can be studied using a variety of techniques, including mass spectrometry, immunoblotting, and immunohistochemistry.

Q7. Can PTMs be targeted for therapeutic purposes?

Ans. Yes, drugs that target specific PTMs have been developed for the treatment of various diseases.

Q8. What is the importance of protein folding in PTMs?

Ans. Protein folding is important in PTMs because the three-dimensional structure of a protein can affect its susceptibility to modification.

Q9. How does the type of amino acid affect the susceptibility of a protein to PTMs?

Ans. The type of amino acid can affect the susceptibility of a protein to PTMs because the chemical properties of the side chains can affect their reactivity.

Q10. Can PTMs be inherited genetically?

Ans. PTMs are not inherited genetically but can be passed down from one generation to another through epigenetic mechanisms such as histone modification.

Updated on: 03-Apr-2023

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