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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. - PowerPoint PPT Presentation
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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)