Protein synthesis, folding, and modification are crucial processes in the production of functional proteins. Proteins are the workhorses of the cell, performing diverse functions such as catalyzing chemical reactions, transporting molecules across membranes, and providing structural support. In order for proteins to carry out their functions, they must be synthesized with the correct amino acid sequence, folded into their correct three-dimensional structure, and sometimes modified post-translationally. In this chapter, we will discuss the key steps involved in protein synthesis, folding, and modification.
Protein synthesis:
Protein synthesis occurs in the ribosomes of the cell, which are made up of RNA and proteins. The process of protein synthesis involves two main steps: transcription and translation.
Transcription:
Transcription is the process by which DNA is used as a template to make RNA. The RNA that is synthesized during transcription is complementary to the DNA template and is called messenger RNA (mRNA). The mRNA is then transported out of the nucleus and into the cytoplasm, where it serves as the template for protein synthesis.
Translation:
Translation is the process by which the amino acid sequence of a protein is determined by the sequence of codons in the mRNA template. The process of translation occurs in the ribosomes, which read the mRNA sequence and use it to synthesize a protein.
The ribosome has two subunits: the small subunit, which reads the mRNA, and the large subunit, which catalyzes the formation of peptide bonds between amino acids. The process of translation involves three main steps: initiation, elongation, and termination.
Initiation:
Initiation begins with the binding of the small ribosomal subunit to the mRNA at the start codon (AUG). The initiator tRNA, which carries the amino acid methionine, binds to the start codon, and the large subunit joins the complex, forming the initiation complex.
Elongation:
During the elongation phase, the ribosome moves along the mRNA, reading each codon and adding the corresponding amino acid to the growing polypeptide chain. Each amino acid is carried to the ribosome by a specific transfer RNA (tRNA) molecule, which recognizes the codon through base pairing between the codon and the anticodon on the tRNA.
The ribosome then catalyzes the formation of a peptide bond between the amino acid on the tRNA in the A site and the growing polypeptide chain in the P site. The ribosome then translocates along the mRNA, moving the tRNA in the A site to the P site and the tRNA in the P site to the E site, where it is released.
Termination:
Termination occurs when the ribosome reaches a stop codon (UAA, UAG, or UGA) on the mRNA. When the ribosome reaches a stop codon, a release factor binds to the ribosome, causing the polypeptide chain to be released from the ribosome.
Protein folding:
After a protein is synthesized, it must fold into its correct three-dimensional structure in order to be functional. The process of protein folding is complex and is not yet fully understood. Proteins fold into their correct structure through a combination of hydrophobic interactions, hydrogen bonds, disulfide bonds, and other interactions.
In order to prevent misfolding, newly synthesized proteins are often assisted by chaperone proteins, which help to guide the protein to its correct structure.
Protein modification:
Protein modification is the process by which proteins undergo changes to their structure or function after they have been synthesized. These modifications can occur at different stages in a protein’s life cycle and can affect various aspects of its activity, stability, localization, and interaction with other molecules.
Post-Translational Modifications
The most common types of protein modifications occur after translation and are referred to as post-translational modifications (PTMs). There are numerous types of PTMs, and some of the most well-known are:
- Phosphorylation: the addition of a phosphate group to specific amino acid residues, usually serine, threonine, or tyrosine. This modification can change a protein’s activity, conformation, localization, and interaction partners.
- Glycosylation: the addition of a sugar moiety to specific amino acid residues, usually asparagine or serine/threonine. This modification can affect a protein’s stability, solubility, trafficking, and interaction with other molecules.
- Acetylation: the addition of an acetyl group to the N-terminus of a protein or specific lysine residues. This modification can affect a protein’s activity, stability, and interaction partners.
- Methylation: the addition of a methyl group to specific amino acid residues, usually lysine or arginine. This modification can affect a protein’s activity, interaction partners, and subcellular localization.
- Ubiquitination: the addition of ubiquitin molecules to specific lysine residues, which can target a protein for degradation or affect its activity, localization, and interaction partners.
Other types of PTMs include proteolytic cleavage, sumoylation, nitrosylation, and lipidation.
Protein Folding and Quality Control
Protein folding is the process by which a newly synthesized protein adopts its native three-dimensional conformation. Protein folding is a complex and delicate process that requires the assistance of molecular chaperones, enzymes, and other factors.
Protein folding is critical for a protein’s function, stability, and interaction with other molecules. Misfolded or partially folded proteins can be toxic to cells and can lead to a variety of diseases, including Alzheimer’s disease, cystic fibrosis, and Huntington’s disease.
To ensure proper protein folding and prevent the accumulation of misfolded proteins, cells have a complex system of quality control mechanisms. These mechanisms include chaperones that assist in protein folding, proteases that degrade misfolded proteins, and autophagy pathways that remove damaged or unwanted proteins.