Podcast
Questions and Answers
Enzymes function effectively at the high pH found inside the lysosome.
Enzymes function effectively at the high pH found inside the lysosome.
False
Proteins can be labeled for degradation by a process called polyubiquitination.
Proteins can be labeled for degradation by a process called polyubiquitination.
True
The proteasome is a hollow, barrel-shaped complex containing protease activity.
The proteasome is a hollow, barrel-shaped complex containing protease activity.
True
Polypeptide chains cannot be modified after translation.
Polypeptide chains cannot be modified after translation.
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Proteolytic cleavage is a process that activates zymogens.
Proteolytic cleavage is a process that activates zymogens.
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Each word of DNA consists of 3 nucleotides, which codes for 2 amino acids.
Each word of DNA consists of 3 nucleotides, which codes for 2 amino acids.
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Phosphorylation of proteins is an unregulated process.
Phosphorylation of proteins is an unregulated process.
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The genetic code is universal and applies to all species.
The genetic code is universal and applies to all species.
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A single amino acid can be coded for by multiple different codons.
A single amino acid can be coded for by multiple different codons.
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Steroid hormone receptors undergo a conformational change upon ligand binding.
Steroid hormone receptors undergo a conformational change upon ligand binding.
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Tyrosine phosphorylation has the least important effects among the amino acids mentioned.
Tyrosine phosphorylation has the least important effects among the amino acids mentioned.
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An insertion of nucleotides causes a frame-shift mutation, which does not affect the remaining sequence.
An insertion of nucleotides causes a frame-shift mutation, which does not affect the remaining sequence.
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Huntington's disease can occur due to amplification of a codon between generations.
Huntington's disease can occur due to amplification of a codon between generations.
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The ribosome is a complex of protein and rRNA.
The ribosome is a complex of protein and rRNA.
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A missense mutation in the β-globin gene involves a single nucleotide substitution that converts a glutamic acid codon to a valine codon.
A missense mutation in the β-globin gene involves a single nucleotide substitution that converts a glutamic acid codon to a valine codon.
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The P site of the ribosome binds incoming aminoacyl tRNA.
The P site of the ribosome binds incoming aminoacyl tRNA.
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TRNA molecules fold into a straight-line structure.
TRNA molecules fold into a straight-line structure.
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Elongation involves the addition of amino acids to the amino end of the growing chain.
Elongation involves the addition of amino acids to the amino end of the growing chain.
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Francis Crick proposed that there must be an adaptor molecule for nucleic acids to interact with amino acids.
Francis Crick proposed that there must be an adaptor molecule for nucleic acids to interact with amino acids.
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The ribosome moves along the mRNA in a 5’ to 3’ direction during translation.
The ribosome moves along the mRNA in a 5’ to 3’ direction during translation.
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The initiator tRNA is located in the A site during the initiation of translation.
The initiator tRNA is located in the A site during the initiation of translation.
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The 'wobble' position refers to the first base in a codon.
The 'wobble' position refers to the first base in a codon.
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There are approximately 61 codons that code for amino acids and about 50 tRNAs.
There are approximately 61 codons that code for amino acids and about 50 tRNAs.
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Peptide bond formation is catalyzed at the peptidyl transferase centre.
Peptide bond formation is catalyzed at the peptidyl transferase centre.
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GTP is required for the final assembly of the ribosome.
GTP is required for the final assembly of the ribosome.
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The ribosome is composed solely of protein.
The ribosome is composed solely of protein.
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The exit site (E site) contains aminoacyl tRNA.
The exit site (E site) contains aminoacyl tRNA.
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Aminoacyl-tRNA is formed when an amino acid is added to the 5' end of the tRNA molecule.
Aminoacyl-tRNA is formed when an amino acid is added to the 5' end of the tRNA molecule.
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Serine is coded by the codon UCC.
Serine is coded by the codon UCC.
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Elongation involves the addition of amino acids to the amino end of the growing chain.
Elongation involves the addition of amino acids to the amino end of the growing chain.
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The ribosome translocation moves by one codon along the mRNA.
The ribosome translocation moves by one codon along the mRNA.
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The peptidyl transferase activity of ribosome is responsible for the termination of protein synthesis.
The peptidyl transferase activity of ribosome is responsible for the termination of protein synthesis.
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The empty tRNA moves into the A site after the peptide bond formation.
The empty tRNA moves into the A site after the peptide bond formation.
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A release factor recognizes a stop codon in the A site during termination.
A release factor recognizes a stop codon in the A site during termination.
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An Open Reading Frame (ORF) can start and end at random positions within a sequence of nucleotides.
An Open Reading Frame (ORF) can start and end at random positions within a sequence of nucleotides.
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The genetic code is non-overlapping, meaning it is read as a continuous sequence from a fixed starting point.
The genetic code is non-overlapping, meaning it is read as a continuous sequence from a fixed starting point.
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Each ‘word’ of DNA consists of 4 nucleotides and codes for 1 amino acid.
Each ‘word’ of DNA consists of 4 nucleotides and codes for 1 amino acid.
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Frame-shift mutations can occur due to insertions or deletions of nucleotides.
Frame-shift mutations can occur due to insertions or deletions of nucleotides.
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Huntington's disease is caused by the deletion of codons in the genetic code.
Huntington's disease is caused by the deletion of codons in the genetic code.
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The genetic code translates nucleic acid sequences to amino acid sequences, where a codon consists of 4 nucleotides.
The genetic code translates nucleic acid sequences to amino acid sequences, where a codon consists of 4 nucleotides.
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In the translation process, termination factors are essential for the proper completion of protein synthesis.
In the translation process, termination factors are essential for the proper completion of protein synthesis.
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MRNA is not required for the process of translation.
MRNA is not required for the process of translation.
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An insertion of nucleotides typically leads to a frame-shift mutation, which can significantly affect the protein's function.
An insertion of nucleotides typically leads to a frame-shift mutation, which can significantly affect the protein's function.
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Phosphorylation of proteins can affect their activity, localization, and function.
Phosphorylation of proteins can affect their activity, localization, and function.
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The ribosome is solely composed of ribosomal proteins without any RNA components.
The ribosome is solely composed of ribosomal proteins without any RNA components.
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The process of elongation in translation involves the addition of amino acids to the carboxyl end of the growing polypeptide chain.
The process of elongation in translation involves the addition of amino acids to the carboxyl end of the growing polypeptide chain.
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Codons can specify more than one amino acid, making the genetic code ambiguous.
Codons can specify more than one amino acid, making the genetic code ambiguous.
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The third base in a codon is known as the 'wobble' position.
The third base in a codon is known as the 'wobble' position.
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Aminoacyl-tRNA is formed when an amino acid is added to the 5' end of the tRNA molecule.
Aminoacyl-tRNA is formed when an amino acid is added to the 5' end of the tRNA molecule.
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Ribosomes are exclusively composed of RNA.
Ribosomes are exclusively composed of RNA.
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There are approximately 50 different tRNA types that correspond to 61 codons coding for amino acids.
There are approximately 50 different tRNA types that correspond to 61 codons coding for amino acids.
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Transfer RNA molecules have a straight-line structure.
Transfer RNA molecules have a straight-line structure.
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Francis Crick suggested that nucleic acids interact with amino acids through a unique structure of adaptor molecules.
Francis Crick suggested that nucleic acids interact with amino acids through a unique structure of adaptor molecules.
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The amino-acid addition process to tRNA is catalyzed by ribosomal RNA.
The amino-acid addition process to tRNA is catalyzed by ribosomal RNA.
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Serine is encoded by the codon UCC according to the genetic code.
Serine is encoded by the codon UCC according to the genetic code.
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The carboxyl end of the growing polypeptide chain is where amino acids are added during elongation.
The carboxyl end of the growing polypeptide chain is where amino acids are added during elongation.
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The P site of the ribosome is where incoming aminoacyl tRNA is first accepted.
The P site of the ribosome is where incoming aminoacyl tRNA is first accepted.
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The initiator tRNA is located in the E site during the initiation of translation.
The initiator tRNA is located in the E site during the initiation of translation.
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During translation, the ribosome moves along the mRNA in the 3’ to 5’ direction.
During translation, the ribosome moves along the mRNA in the 3’ to 5’ direction.
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Recognition of the start codon by the tRNA is essential for the initiation of translation.
Recognition of the start codon by the tRNA is essential for the initiation of translation.
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GTP is not required during the initiation of translation.
GTP is not required during the initiation of translation.
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The ribosome has a specific site known as the decoding center for accepting tRNAs.
The ribosome has a specific site known as the decoding center for accepting tRNAs.
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During elongation, after forming a peptide bond, the ribosome translocates three nucleotides in the 5’ direction.
During elongation, after forming a peptide bond, the ribosome translocates three nucleotides in the 5’ direction.
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During ribosome translocation, the peptidyl chain is moved to the A site.
During ribosome translocation, the peptidyl chain is moved to the A site.
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Peptidyl transferase activity involves the formation of peptide bonds at the P site.
Peptidyl transferase activity involves the formation of peptide bonds at the P site.
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Termination of translation occurs when a release factor binds to the A site.
Termination of translation occurs when a release factor binds to the A site.
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The path through the ribosome for each tRNA is A – E – P sites.
The path through the ribosome for each tRNA is A – E – P sites.
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Each elongation step involves the binding of a new aminoacyl tRNA in the P site.
Each elongation step involves the binding of a new aminoacyl tRNA in the P site.
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The lysosome contains degradative enzymes that specifically target proteins only.
The lysosome contains degradative enzymes that specifically target proteins only.
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Regulating protein activity solely relies on the protein synthesis process, without any involvement of degradation.
Regulating protein activity solely relies on the protein synthesis process, without any involvement of degradation.
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Cyclins are examples of proteins that undergo rapid turnover to control the cell cycle progression.
Cyclins are examples of proteins that undergo rapid turnover to control the cell cycle progression.
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Protein levels, protein location, and post-translational modification are the only methods used by a cell to regulate protein activity.
Protein levels, protein location, and post-translational modification are the only methods used by a cell to regulate protein activity.
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Protein degradation is an unnecessary process and does not contribute to cellular homeostasis.
Protein degradation is an unnecessary process and does not contribute to cellular homeostasis.
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The proteasome is found exclusively in the nucleus and cannot be located in the cytoplasm.
The proteasome is found exclusively in the nucleus and cannot be located in the cytoplasm.
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Proteins can undergo various covalent modifications after translation, including glycosylation.
Proteins can undergo various covalent modifications after translation, including glycosylation.
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Steroid hormone receptors require a conformational change to release their inhibitory subunits.
Steroid hormone receptors require a conformational change to release their inhibitory subunits.
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Reversible phosphorylation can occur on all amino acid residues in a protein equally.
Reversible phosphorylation can occur on all amino acid residues in a protein equally.
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Zymogens are active forms of enzymes that do not require activation by cleavage.
Zymogens are active forms of enzymes that do not require activation by cleavage.
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The ratio of phosphorylated serine to threonine to tyrosine residues is approximately 10:1:100.
The ratio of phosphorylated serine to threonine to tyrosine residues is approximately 10:1:100.
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Ligand binding to a protein does not alter the protein's shape or its active conformation.
Ligand binding to a protein does not alter the protein's shape or its active conformation.
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Proteolytic cleavage does not play a role in the processing of insulin from its precursor form.
Proteolytic cleavage does not play a role in the processing of insulin from its precursor form.
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An Open Reading Frame (ORF) is a set of codons that runs continuously and always begins with a stop codon.
An Open Reading Frame (ORF) is a set of codons that runs continuously and always begins with a stop codon.
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The genetic code is redundant, meaning multiple codons can code for the same amino acid.
The genetic code is redundant, meaning multiple codons can code for the same amino acid.
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A single nucleotide insertion in a DNA sequence will always create a frame-shift mutation.
A single nucleotide insertion in a DNA sequence will always create a frame-shift mutation.
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The phenomenon of codon amplification can lead to increased severity of diseases such as Huntington's disease.
The phenomenon of codon amplification can lead to increased severity of diseases such as Huntington's disease.
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The genetic code is specific and applies only to a limited number of species.
The genetic code is specific and applies only to a limited number of species.
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The A site of the ribosome binds deacylated tRNA during translation.
The A site of the ribosome binds deacylated tRNA during translation.
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During elongation, peptide bonds are formed between adjacent amino acids at the P site.
During elongation, peptide bonds are formed between adjacent amino acids at the P site.
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Recognition of the start codon by the tRNAmet molecule is crucial for the initiation of translation.
Recognition of the start codon by the tRNAmet molecule is crucial for the initiation of translation.
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The ribosome moves along mRNA in a 3’ to 5’ direction during translation.
The ribosome moves along mRNA in a 3’ to 5’ direction during translation.
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Initiation factors are not required for the ribosome to recognize the start of translation.
Initiation factors are not required for the ribosome to recognize the start of translation.
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The 60S ribosomal subunit assembles with the 40S subunit during the final assembly of translation.
The 60S ribosomal subunit assembles with the 40S subunit during the final assembly of translation.
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Elongation involves moving the ribosome three nucleotides at a time along the mRNA.
Elongation involves moving the ribosome three nucleotides at a time along the mRNA.
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The decoding center ensures that only tRNAs with anticodons that match the codon are rejected.
The decoding center ensures that only tRNAs with anticodons that match the codon are rejected.
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The tRNA molecules typically have a cloverleaf secondary structure.
The tRNA molecules typically have a cloverleaf secondary structure.
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There are 61 tRNA molecules that correspond to the 61 different coding codons.
There are 61 tRNA molecules that correspond to the 61 different coding codons.
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The anti-codon loop of tRNA pairs with mRNA codons based on non-specific rules.
The anti-codon loop of tRNA pairs with mRNA codons based on non-specific rules.
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A single tRNA species can recognize only one specific codon.
A single tRNA species can recognize only one specific codon.
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The aminoacyl-tRNA is formed by the addition of an amino acid to the 3' end of the tRNA molecule.
The aminoacyl-tRNA is formed by the addition of an amino acid to the 3' end of the tRNA molecule.
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Francis Crick theorized that there would be 20 different types of transfer RNA molecules due to the 20 amino acids.
Francis Crick theorized that there would be 20 different types of transfer RNA molecules due to the 20 amino acids.
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Transfer RNA does not undergo any post-transcriptional modifications.
Transfer RNA does not undergo any post-transcriptional modifications.
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The ribosome is involved solely in the synthesis of nucleic acids.
The ribosome is involved solely in the synthesis of nucleic acids.
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Study Notes
Lysosomes
- Enzymes within lysosomes function optimally at a low pH.
Proteasome
- Proteins targeted for degradation are labelled with a polyubiquitin tag.
- The proteasome recognizes this tag and degrades the protein.
- The proteasome is a multiprotein complex with protease activity.
Post-Translational Modification
- Modifications occur after translation to form mature functional proteins.
- Proteolytic cleavage removes sections of a protein, for example, in the processing of insulin and activation of trypsinogen.
- Covalent modifications include disulfide bond formation, phosphorylation, glycosylation, farnesylation, and GPI anchoring.
Ligand Binding
- Ligands can induce conformational changes in proteins, activating them, releasing inhibitory subunits, or altering their cellular location.
- Steroid hormone receptors undergo conformational change upon binding to their steroid ligand.
- This change allows the receptor to dimerize and enter the nucleus.
Proteolytic Cleavage
- Zymogens are inactive 'pro-enzymes' activated by proteolytic cleavage.
- Enterokinase is an example of an enzyme that activates zymogens.
- Proteolytic cascades, like the clotting cascade, involve a series of sequential proteolytic cleavage events.
Reversible Phosphorylation
- Phosphorylation of proteins on serine, threonine, and tyrosine residues is a tightly regulated process.
- Kinases add phosphate groups, while phosphatases remove them.
- Tyrosine phosphorylation plays a critical role in cellular signaling and regulation.
The Genetic Code
- The genetic code is non-overlapping, meaning codons are read in a continuous sequence.
- The 'reading frame' is defined by the start codon, and only one open reading frame (ORF) in a sequence contains functional information.
- Insertions or deletions within a sequence can cause 'frame-shift' mutations.
The Genetic Code: Properties
- Specific: Each codon always codes for the same amino acid.
- Universal: The code is largely the same across all species.
- Redundant: Multiple codons can code for the same amino acid.
- Non-overlapping: The code is read as a continuous sequence of bases, three at a time.
Disease and Coding Sequence Changes
- Huntington's disease results from the amplification of CAG codons in the HTT gene, causing an increased number of glutamine residues in the protein.
- Sickle Cell Disease (SCD) is caused by a single nucleotide substitution in the beta-globin gene, changing a glutamic acid codon to a valine codon.
tRNA
- tRNA molecules serve as adaptor molecules, translating the genetic code.
- These molecules fold into an L-shaped structure with a specific 3-dimensional shape.
- Aminoacyl-tRNA synthetases attach amino acids to the 3' end of tRNA, forming aminoacyl-tRNAs.
- The anticodon loop on tRNA interacts with codons in mRNA through base-pairing.
Wobble Position
- The third base in a codon is called the wobble position, allowing for flexibility in codon-anticodon matching.
- A single tRNA can often recognize multiple codons for the same amino acid.
Ribosomes
- Ribosomes are essential for protein synthesis.
- They consist of ribosomal RNA (rRNA) and proteins.
- Ribosomes bring mRNA and tRNA together during translation.
Ribosome Structure
- The ribosome has three sites: A site for aminoacyl tRNA, P site for the growing polypeptide chain, and E site for exiting tRNA.
- The decoding center ensures only codons matching tRNA anticodons enter the A site.
- Peptidyl transferase activity catalyzes peptide bond formation.
Translation Initiation
- Initiation requires the assembly of ribosomal subunits, mRNA, initiator tRNA (tRNAmet), GTP, and initiation factors.
- Recognition of the start codon by the tRNAmet molecule is crucial.
- The 60S ribosomal subunit joins the 40S subunit to complete the complex.
Translation Elongation
- Amino acids are added to the growing polypeptide chain in the carboxyl-terminal direction.
- The ribosome moves along the mRNA in the 5' to 3' direction.
- Elongation involves three steps:
- Delivery of the next aminoacyl-tRNA to the A site.
- Peptide bond formation between adjacent amino acids.
- Ribosome translocation to the next codon.
Translation Termination
- Termination occurs when a stop codon enters the A site.
- Release factors bind to the stop codon, causing:
- Release of the newly synthesized polypeptide chain.
- Dissociation of the ribosomal subunits and mRNA.
Information Flow
- The Central Dogma of Molecular Biology describes the flow of genetic information from DNA to RNA to protein.
- Coined by Francis Crick in 1956.
Overview of Translation
- Translation is the process of converting the information in mRNA into amino acids, resulting in protein synthesis.
- Consists of three stages: initiation, elongation, and termination.
Translation Requirements
- Template: mRNA carries the genetic code.
- Catalyst: Ribosome, composed of ribosomal proteins and rRNA, facilitates the process.
- Activated Precursors: Aminoacyl-tRNA, tRNA molecules coupled to amino acids via energy-rich bonds.
- Release/Termination Factors: Assist in terminating the translation process.
The Genetic Code
- The genetic code is the dictionary for translating DNA sequences into amino acids.
- Each three-nucleotide sequence (codon) in mRNA corresponds to a specific amino acid.
- The code is unpunctuated, meaning it's read continuously without gaps.
Reading Frames
- Open Reading Frame (ORF): A continuous sequence of codons beginning with a start codon and ending with a stop codon.
- The 'reading frame' is determined by the position of the start codon.
- In protein synthesis, only one ORF is essential for information.
- Insertions or deletions of nucleotides can cause "frame-shift" mutations, altering the reading frame and potentially changing the encoded protein.
The Genetic Code: Specific, Universal, Redundant, Non-Overlapping
- Specific: Each codon always codes for the same amino acid.
- Universal: Applies to all species, conserved from early evolution.
- Redundant: A given amino acid can be specified by several codons.
- Non-Overlapping: The code is read continuously as a sequence of bases, taken three at a time.
Changes in Coding Sequence and Disease
- Huntington's Disease: Caused by amplified codons, leading to extra amino acids and altered protein structure, potentially accumulating in the cell.
- Sickle Cell Disease (SCD): A missense mutation in the β-globin gene, a single nucleotide substitution resulting in an amino acid change from glutamic acid to valine.
tRNA: The Adaptor Molecule
- tRNA acts as an adaptor molecule, bridging the gap between nucleic acids and proteins.
- Proposed by Francis Crick, with 20 different adaptors for each amino acid.
- tRNA folds into an L-shaped structure due to base-pairing between nucleotides.
- The amino acid is added to the 3' end of the tRNA molecule to give an aminoacyl-tRNA by aminoacyl-tRNA synthetase.
- The anticodon loop on tRNA recognizes codons within the mRNA through base-pairing.
The Wobble Position
- The third base in a codon (first in the anticodon) is known as the "wobble position". Provides flexibility in codon recognition allowing a single tRNA to match multiple codons.
Ribosome: The Protein Synthesis Factory
- Ribosomes are complexes of proteins and rRNA, essential for protein synthesis.
- They bind tRNA and mRNA together to translate the nucleotide sequence of mRNA into the amino acid sequence of a protein.
Ribosome Structure
- A (aminoacyl) site: Binds incoming aminoacyl-tRNA.
- P (peptidyl) site: Contains tRNA with the growing polypeptide chain.
- E (exit) site: Holds deacylated tRNA before release.
- Decoding center: Ensures only matching tRNAs are accepted.
- Peptidyl transferase center: Catalyzes peptide bond formation.
Initiation of Translation
- Requires the assembly of components: 40s ribosomal subunit, mRNA, tRNAmet (initiator tRNA), GTP, and initiation factors.
- Recognition of the start codon by tRNAmet.
- Addition of the 60s ribosomal subunit to complete the assembly.
Elongation of Translation
- Involves adding amino acids to the carboxyl end of the growing chain.
- The ribosome moves along the mRNA in the 5' to 3' direction.
- Requires aminoacyl-tRNA delivery to the A site, peptide bond formation by peptidyl transferase, and ribosome translocation to the next codon.
Termination of Translation
- Occurs when a stop codon reaches the A site.
- Recognized by a release factor that binds to the A site, causing the release of the newly synthesized protein and detaching the ribosome from the mRNA.
Disassembly of the tRNA-ribosome-mRNA complex
- Ribosomal subunits, mRNA, tRNA and protein factors can be recycled and used to make additional proteins.
Regulation of Protein Activity
- Many key functions that occur in cells are dependent on the activities of proteins.
- Regulating protein activity is essential for maintaining cellular function.
Regulation of Protein Activity: Mechanisms
- Protein Levels: Regulating the amount of protein produced.
- Protein Location: Controlling where a protein is located within the cell.
- Post-translational Modification: Modifying proteins after translation to alter their activity.
Balancing Protein Synthesis with Degradation
- Protein turnover is a natural process.
- "Housekeeping" proteins are damaged and need to be replaced.
- Some proteins involved in cellular processes are degraded for tight control over their levels.
- Rapid turnover of some proteins allows for changes in their levels.
Protein Degradation Mechanisms
-
Lysosomal Degradation: Lysosomes are membrane-bound organelles containing degradative enzymes.
- These enzymes degrade proteins, other molecules, organelles, microbes, and materials delivered to the lysosome.
- Enzymes function optimally in the low pH environment of the lysosome.
-
Proteasomal Degradation: Proteins can be tagged for degradation by polyubiquitination.
- Polyubiquitinated proteins are recognized by the proteasome and degraded.
- Proteasome: A multiprotein, hollow, barrel-shaped complex containing protease activity.
- Found in the nucleus and cytoplasm.
- Protein "caps" on the proteasome recognize tagged proteins and feed them into the proteasome for degradation.
Polypeptide Chain Modifications After Translation
-
Proteolytic Cleavage: Processing of proteins from immature to mature forms.
- Example: Processing of insulin from pre-pro insulin to mature insulin.
- Example: Trypsinogen to trypsin.
-
Covalent Modifications: Modifications that alter the protein's structure and function.
- Disulfide Bond Formation: Stabilizes protein structure.
- Phosphorylation: Often activates or inactivates proteins. Important control mechanism.
- Glycosylation: Often found in extracellular proteins.
- Farnesylation and GPI Anchoring: Target proteins to membranes.
Ligand Binding
- Ligands bind to proteins and induce conformational changes.
- This allows for activation, inhibition, or relocation of proteins.
- Example: Steroid hormone receptors bind their ligands, undergo conformational changes, dimerize, and enter the nucleus.
Proteolytic Cleavage
- Zymogens: Inactive precursor forms of enzymes (pro-enzymes).
- Activated by proteolytic cleavage.
- Example: Enterokinase activates trypsinogen to trypsin.
- Proteolytic cascades: Series of proteolytic cleavages, often involved in complex processes like blood clotting.
Reversible Phosphorylation of Proteins
- Phosphate groups can be added to serine, threonine, and tyrosine residues.
- Tightly regulated process.
- Kinases add phosphate groups, phosphatases remove them.
- Ratio of phosphorylated serine:threonine:tyrosine is approximately 100:10:1.
- Tyrosine phosphorylation often has significant effects on protein activity.
Genetic Code: Introduction
- The genetic code specifies the relationship between codons (three-nucleotide sequences) and amino acids.
- If one nucleotide coded for one amino acid, there would be 4 possibilities.
- Two nucleotides would provide 16 possibilities (4 x 4).
- Three nucleotides provide 64 possibilities (4 x 4 x 4).
- Each "word" of DNA consists of three nucleotides/bases, which code for one amino acid.
The Genetic Code: Properties
-
Unpunctuated: Reading frames determine the sequence of amino acids.
- Open Reading Frame (ORF): A continuous set of codons starting with a start codon and ending with a stop codon.
- The reading frame is determined by the position of the start codon.
- Only one ORF contains useful information for protein synthesis.
-
Specific: A specific codon always codes for the same amino acid.
-
Universal: The code applies to all species. Conserved from early evolution.
-
Redundant: A given amino acid can be coded for by several different codons.
-
Non-overlapping: The code is read from a fixed starting point as a continuous sequence of bases, taken three at a time.
Genetic Code and Disease: Huntington's Disease
- Codon amplification can occur between generations.
- Each extra codon copy leads to an extra copy of the amino acid in the protein.
- This can alter protein structure and lead to accumulation and deposition of the protein in the cell.
Genetic Code and Disease: Sickle Cell Disease (SCD)
- Missense mutation in the β-globin gene.
- A single nucleotide substitution (A to T) in the codon for amino acid 6.
- Converts a glutamic acid codon (GAG) to a valine codon (GTG).
- Autosomal recessive inheritance.
tRNA: The Adaptor Molecule
- Nucleic acids and proteins are structurally different.
- Francis Crick proposed "adaptor molecules" to bridge this gap: These molecules would bind to amino acids and recognize specific codons in mRNA.
- tRNA is the adaptor molecule.
tRNA Properties
- tRNA molecules fold into L-shaped structures.
- Secondary structure: "Cloverleaf" shape due to base pairing.
- Tertiary structure: L-shaped three-dimensional shape.
- Post-transcriptional modifications occur in tRNA molecules.
- Amino acid is added to the 3' end of the tRNA molecule by aminoacyl-tRNA synthetase.
- Specificity derives from the 3D structure of the tRNA.
- The "anticodon loop" of tRNA recognizes codons in mRNA through base pairing following Watson-Crick rules.
- ~80 nucleotides in length.
- About 50 different tRNA molecules exist.
tRNA Anticodon and mRNA Codon Pairing
- tRNA anticodons pair with mRNA codons following Watson-Crick base pairing rules.
- Example: UCC codes for Serine.
The "Wobble" Position
- The 3rd base in a codon is the "wobble" position.
- Allows for flexibility in codon-anticodon pairing.
- A single tRNA species can recognize multiple codons.
The Ribosome
- Ribosomes are the protein synthesis machinery.
- Composed of protein and ribosomal RNA (rRNA).
- rRNA has extensive secondary structuring, similar to tRNA.
- Brings tRNA and mRNA together to translate the nucleotide sequence of mRNA into the amino acid sequence of a protein.
Ribosome Structure
- A site: Aminoacyl site, binds incoming aminoacyl-tRNA.
- P site: Peptidyl site, holds the tRNA containing the growing polypeptide chain.
- E site: Exit site, where the deacylated tRNA exits the ribosome.
- Decoding center: Ensures only tRNAs with the correct anticodon are accepted into the A site.
- Peptidyl transferase center: Catalyzes peptide bond formation between amino acids.
Initiation of Translation: Requirement
-
Assembly of components for protein synthesis:
- 40S ribosomal subunit
- mRNA to be translated
- tRNA specified by the first codon in the mRNA (tRNAmet)
- GTP (energy source)
- Initiation factors (help the ribosome recognize the start of translation)
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Recognition of the start codon by tRNAmet.
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Addition of the 60S ribosomal subunit to complete the ribosome assembly.
Initiation of Translation: Steps
- Step 1: Initial assembly of components.
- Step 2: Recognition of the start codon.
-
Step 3: Final assembly of the ribosome.
- The initiator tRNA is in the P site.
Elongation: Building the Polypeptide Chain
-
Elongation involves adding amino acids to the carboxyl end of the growing polypeptide chain.
-
Ribosome moves along the mRNA in the 5' to 3' direction.
-
Step 1: The next required aminoacyl-tRNA is delivered to the A site (with help of elongation factors).
-
Step 2: Peptide bond formation between adjacent amino acids, catalyzed by peptidyltransferase.
-
Step 3: Translocation: Ribosome moves three nucleotides in the 3' direction to the next codon.
- The growing chain moves to the P site.
- The uncharged tRNA moves to the E site and is released.
- The A site is free to accept the next tRNA.
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Note: The P site initially contains the initiator tRNA.
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This quiz explores the functions of lysosomes and proteasomes in cellular processes, including details on enzyme activity, protein degradation, and post-translational modifications. Test your understanding of how ligand binding affects protein functionality and cellular localization.
