Molecular Biology: Translation and Genetics

Translation Overview

• Translation is the synthesis of proteins
• It involves nucleic acids, DNA replication, and transcription
• It's a crucial process in the central dogma of molecular biology

The Genetic Code

• Proteins, with 20 different amino acids, are coded by mRNA sequences containing only 4 nucleotides
• A codon is a sequence of 3 nucleotides encoding an amino acid
• There are 64 possible combinations of codons

Codon Table

• A table with 3 positions (First, Second, Third) to decode codons
• Different codons translate into specific amino acids

Reading Frames

• mRNA sequence can be read in different ways (frames 1-3)
• This sequence impacts the amino acid sequence of the protein
• Alterations through insertion or deletion mutations produce frame-shift mutations resulting in inaccurate amino acid sequences

Point Mutations

• Point mutations change a single nucleotide in the DNA sequence and may be altered to a different amino acid (missense) or a stop codon (nonsense)
• Point mutations can be silent if they change the codon to a synonymous codon that codes for the same amino acid

Trinucleotide Repeat Expansion

• Mutations where a sequence of 3 bases is amplified
• Results in extra amino acids within the coding region
• Can lead to neurodegenerative disorders or reduced protein production in non-coding regions, like Huntington's disease

Cystic Fibrosis

• A mutation in a gene coding for a protein (CFTR) leads to the malfunction of CFTR destroying the protein
• The deletion of 3 nucleotides in the CFTR gene often results in a loss of phenylalanine at position 508

Protein Synthesis Requirements

• Translation requires amino acids, tRNA, aminoacyl-tRNA synthetases, mRNA, ribosomes, protein factors, and energy (ATP and GTP)

tRNA Structure

• tRNA carries amino acids to the ribosome for protein synthesis
• It includes an anticodon sequence that base-pairs with the mRNA codon
• It has an amino acid attachment site

Aminoacyl-tRNA Synthetase

• Enzymes that accurately attach the correct amino acids to their corresponding tRNA molecules
• This activation of amino acids is an energy-intensive step

Eukaryotic Ribosome

• Ribosomes are the site of protein synthesis
• Composed of rRNA and ribosomal proteins
• Have binding sites for tRNA molecules carrying amino acids
• Found in the cytoplasm or associated with the rough endoplasmic reticulum

Peptide Bond Formation

• Peptidyl transferase catalyzes the formation of peptide bonds between amino acids
• It's an enzyme within the ribosome, where the growing polypeptide chain is extended

Steps in Protein Translation (Initiation, Elongation, Termination)

• Initiation involves assembly of components to begin translation
• Elongation steps include adding amino acids to the growing polypeptide chain
• Termination occurs when a stop codon is reached; signaling the release of the completed polypeptide chain

Post-translational Modifications

• Trimming, Phosphorylation, glycosylation, hydroxylation, and carboxylation or acetylation, and addition of farnesyl groups are some post-translational alterations

Energy in Protein Synthesis

• 4 high-energy bonds are used per amino acid addition
• These energies are required for aminoacyl-tRNA binding to the ribosome and ribosome translocation

Medical Relevance

• Antibiotics like streptomycin, tetracyclines, and puromycin bind to prokaryotic ribosomes to inhibit bacterial protein synthesis
• Diphtheria toxin inhibits eukaryotic protein synthesis

Additional Resources

• Several YouTube videos are suggested for further learning