Gene Expression: Translation

Chapter 6 Gene Expression: Translation

• Overview
  • Focus on the processes involved in translation, converting genetic information from mRNA into a polypeptide chain.
  • Relevant study questions at the end of the chapter are aligned with this content.

Amino Acids and Their Structure

• α-carbon atom: Central to all amino acids with four substituents:

  • H: Hydrogen atom
  • Amino group (-NH2): Donates an H+, making it a basic unit
  • Carboxyl group (-COOH): Provides acidity
  • R group: Varies per amino acid, determining chemical properties.

• Structures common to all amino acids:

             H   
             |   
        H - N+ - C - COO-   
             |   
             R   

Classification of Amino Acids

• Amino acids can be classified based on their side chains (R groups):

  • Basic (positively charged):
  • Lysine (Lys - K): H3N+-CH2-(CH2)2-NH3
  • Arginine (Arg - R): H3N+-CH2-(CH2)2-C(NH2)=N-
  • Histidine (His - H): Variable charge depending on pH
  • Acidic (negatively charged):
  • Aspartic Acid (Asp - D): -COO-
  • Glutamic Acid (Glu - E): -COO-
  • Polar Neutral:
  • Serine (Ser - S): -CH2-OH
  • Asparagine (Asn - N): -CH2-C(=O)NH2
  • Non-Polar:
  • Alanine (Ala - A): -CH3
  • Valine (Val - V): -C(CH3)2

• Examples of amino acids:

  • Glycine (Gly - G): Simplest amino acid, with H as R group.
  • Tryptophan (Trp - W) and Phenylalanine (Phe - F): Aromatic amino acids.

Formation of Amino Acid Chains

• Translation involves the following steps:
  • The genetic code is transcribed from DNA to mRNA.
  • mRNA is translated on the ribosomes into a polypeptide chain.
  • Peptide bond formation occurs, joined by the enzyme peptidyl transferase.

Levels of Protein Structure

• Primary structure: Sequence of amino acids in a polypeptide chain.
• Secondary structure: Folding and twisting into structures like alpha-helices and beta-pleated sheets.
• Tertiary structure: Overall three-dimensional shape of a folded polypeptide.
• Quaternary structure: The arrangement of multiple polypeptide chains, such as in hemoglobin (2 alpha and 2 beta chains).

tRNA Structure

• Cloverleaf model of tRNA
  • Anticodon loop: Recognizes the codon on mRNA.
  • Amino acid attachment: tRNA carries amino acids at its 3' end.
  • L-shaped 3D structure: Indicates the spatial arrangement for interaction with ribosomes.

Codon Usage

• Codons are three-nucleotide sequences on mRNA that dictate amino acid placement:
  • Example Codon usages:
  • UUU → Phenylalanine (Phe)
  • UAC → Tyrosine (Tyr)
  • AUG → Methionine (Met), also the start codon.
  • Wobble hypothesis: Explains flexibility in base pairing at the third position of the codon.

Aminoacyl-tRNA Synthetase Mechanism

• Facilitates attachment of amino acids to tRNA.
• Reactions include:
  • Amino acid and ATP bind to the enzyme, forming aminoacyl-AMP.
  • Transfer of the amino acid to tRNA, creating charged aminoacyl-tRNA (aa-tRNA).

Translation Phases

• Initiation: The start process of translation begins at the start codon (AUG on mRNA).
  • Requires several initiation factors in eukaryotes (eIFs) and forms the initiation complex at the ribosome.
• Elongation: Amino acids are sequentially added to the growing polypeptide chain.
  • Involves the binding of aminoacyl-tRNA to the A site, peptide bond formation at P site, and movement of tRNA and mRNA.
• Termination: Occurs when the ribosome reaches a stop codon (UAA, UAG, or UGA).
  • Release factors (RF1, RF3) bind to the ribosome, promoting polypeptide release and ribosomal disassembly.

Ribosome Structure

• Eukaryotic Ribosome: Composed of a large (60S) and small subunit (40S).
  • Defines distinct sites for tRNA binding: Aminoacyl (A), Peptidyl (P), and Exit (E) sites, facilitating translation.
• Prokaryotic Ribosome: Slightly smaller (50S and 30S).

Stop Codon Recognition and Release

• When a stop codon is encountered:
  • Release factor binds to the ribosome, displacing the completed polypeptide chain from the P site.
  • Ribosomes recycle back to their individual subunits ready for a new mRNA transcript.

Protein Trafficking and Sorting

• Process occurs within the cell as polypeptides exit ribosomes:
  • Signal peptide emerges from ribosome, recognized by signal recognition particle (SRP).
  • SRP binds to its receptor in the endoplasmic reticulum (ER) to facilitate further processing.
• Completed polypeptide is released into the ER lumen for further modifications.

Endosymbiotic Theory

• Describes the origin of eukaryotic cells, explaining how they evolved from prokaryotic ancestors through a series of steps including:
  1. Formation of an early endomembrane system from prokaryotic cells.
  2. Aerobic bacteria being engulfed as endosymbionts leading to the creation of mitochondria.
  3. Later acquisition of chloroplasts from cyanobacteria by some eukaryotes.