Genetic Code
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Transcript of Genetic Code
Genetic Code
• Codons composed of three nucleotides in RNA• Codon specifies amino acid or stop• Genetic code is redundant
Genetic Code Table
Reading Frames
• One of three possible reading frames contains protein message
Mutations In Protein-Coding Sequences
Missense Change to codon for different amino acid
Silent Change to codon for same amino acid
Nonsense Change to stop codon
Insertion/ Usually disrupt reading framedeletion
• Adaptors for associating codons with amino acids• Cloverleaf structure• Anticodon recognizes codon by complementary
base-pairing
Transfer RNA
Wobble Base-pairing
• Relaxed base-pairing at third position of codon
• tRNA may recognize multiple codons
Modified Nucleotides In tRNA
• post-transcriptional modifications
• Different synthetase for each amino acid• Amino acid attached to tRNA by high
energy ester bond
Aminoacyl-tRNA Synthetases
Sequential Action Of Adaptors
Editing By Synthetases
• Active site may mistakenly bind related amino acid• Incorrect amino acid is hydrolyzed at editing site
Growth Of Polypeptide
•Stepwise growth from N-terminus to C-terminus
• Large and small subunits• Composed of rRNA and proteins
Ribosome Structure
Translation On Ribosome
• P site contains tRNA attached to growing polypeptide
• A site binds incoming aminoacyl-tRNA
• Peptide bond formation by peptidyl transferase of ribosome
• Translocation of ribosome
• EF-Tu:GTP interacts with A site
• Codon-anticodon interaction leads to hydrolysis of GTP and dissociation of EF-Tu
• EF-G promotes ribosome translocation
Elongation Factors
Diphtheria Toxin
• Transfer of adenosine diphosphate ribose to EF-2
• Inhibits EF-2, which impairs ribosome translocation
Initiation In Eucaryotes
• Methionine-linked initiator tRNA to small ribosome P site (eIF-2)
• Load onto mRNA 5’ end (eIF-4E, eIF-4G, polyA)
• Scan for AUG• Assemble large
ribosomal subunit
Initiation In Bacteria
• Formylmethionine-linked initiator tRNA• Small ribosome subunit binds to Shine-Dalgarno sequence• Polycistronic mRNAs
Termination
• Stop codons not recognized by tRNA• Release factors bind to A site• Addition of H2O to peptidyl-tRNA
Polyribosomes
• Multiple ribosomes translating same mRNA
• Interaction of mRNA 5’ and 3’ ends
Selenocysteine
• Selenocysteine tRNA is charged with serine that is subsequently converted
• Encoded by UGA codon followed by special signal
Antibiotics
Tetracycline blocks binding of aminoacyl- tRNA to A-site of ribosome
Streptomycin prevents the transition from initiation complex to chain-elongating
ribosome; causes miscodingChloramphenicol blocks the peptidyl transferase reaction on ribosomesErythromycin blocks the translocation reaction on
ribosomesRifamycin blocks initiation of RNA chains by
binding to RNA polymerase
Folding During Synthesis
• Individual domains folded rapidly after their synthesis
Creating Functional Proteins
• Association with cofactors, proteins
• Covalent modifications
Molecular Chaperones
• Prevent inappropriate aggregation during folding• Recognize exposed hydrophobic regions• Hydrolyze ATP• Heat shock proteins
Hsp70 Chaperones
• Act early• Repeated cycles of target binding & release
mediated by ATP binding & hydrolysis
Hsp60 Chaperones
• Chaperonins• Isolation chambers• Cycles of target confinement & release
mediated by ATP binding & hydrolysis
Protein Quality Control
• Exposed hydrophobic regions indicate misfolding• Selective degradation of proteins that cannot be
correctly folded
Proteasome
• Protease activity in interior of cylinder
• Caps function in ATP-dependent unfolding and as gates for selective entry
Attachment Of Ubiquitin
• Attached to lysine on target; multiubiquitin chains• Ubiquitin attaches to E1• Transferred to E2 of ubiquitin ligase• E3 of ubiquitin ligase recognizes degradation signal
Regulated Degradation
• Modification of an E3 protein
• Modification of a target protein
Disease From Protein Aggregation
• Aggregates of misfolded proteins
• Cross-beta filaments• Neurodegeneration-
Huntington’s, Alzheimer’s, Prion diseases (Creutzfeldt-Jacob, bovine spongiform encephalopathy)