Genetic information flows from mrn to protein through the process of translation
TYPES OF RN (RIBONUCLEIC CID) RN s job - protein synthesis (assembly of amino acids into proteins) Three main types: 1. Messenger RN- serve as messengers from DN to the rest of the cell 2. Ribosomal RN- combines with proteins to form ribosomes 3. Transfer RN - translates the three-letter codon of mrn to the amino acids that make up proteins
Coded message on mrn is translated into a protein structure Occurs at the ribosome Ribosome reads mrn code trn molecules bring in amino acid monomers (building blocks) mrn codons match trn anticodons to ensure the correct sequence of amino acids in the protein
Polypeptide mino acids Ribosome trn with amino acid attached trn C G nticodon U G G U U U G G C Codons mrn
Molecules of trn are not identical Each carries a specific amino acid on one end Each has an anticodon on the other end; the anticodon base-pairs with a complementary codon on mrn
mino acid attachment site mino acid attachment site Hydrogen bonds Hydrogen bonds nticodon (a) Two-dimensional structure nticodon (b) Three-dimensional structure G nticodon (c) Symbol used in this book
minoacyl-trn synthetase (enzyme) mino acid P denosine P P P denosine TP P i P P i P i trn minoacyl-trn synthetase trn mino acid P denosine MP Computer model minoacyl trn ( charged trn )
Ribosomes facilitate specific coupling of trn anticodons with mrn codons in protein synthesis The two ribosomal subunits (large and small) are made of proteins and ribosomal RN (rrn) Bacterial and eukaryotic ribosomes are somewhat similar but have significant differences: some antibiotic drugs specifically target bacterial ribosomes without harming eukaryotic ribosomes
trn molecules Growing polypeptide Exit tunnel E P Large subunit Small subunit mrn (a) Computer model of functioning ribosome
ribosome has three binding sites for trn The P site holds the trn that carries the growing polypeptide chain The site holds the trn that carries the next amino acid to be added to the chain The E site is the exit site, where discharged trns leave the ribosome
P site (Peptidyl-tRN binding site) Exit tunnel E site (Exit site) site (minoacyltrn binding site) E P Large subunit mrn binding site Small subunit (b) Schematic model showing binding sites
mino end Growing polypeptide Next amino acid to be added to polypeptide chain mrn E trn Codons (c) Schematic model with mrn and trn
The three stages of translation Initiation Elongation Termination ll three stages require protein factors that aid in the translation process
The initiation stage of translation brings together mrn, a trn with the first amino acid, and the two ribosomal subunits First, a small ribosomal subunit binds with mrn and a special initiator trn Then the small subunit moves along the mrn until it reaches the start codon (UG) Proteins called initiation factors bring in the large subunit that completes the translation initiation complex
Initiator trn mrn Start codon mrn binding site U C U G GTP Small ribosomal subunit P i + GDP P site E Large ribosomal subunit Translation initiation complex
During the elongation stage, amino acids are added one by one to the preceding amino acid at the C- terminus of the growing chain Each addition involves proteins called elongation factors and occurs in three steps: codon recognition, peptide bond formation, and translocation Translation proceeds along the mrn in a 5ʹ to 3ʹ direction
mino end of polypeptide Ribosome ready for next aminoacyl trn mrn E P site site GTP GDP + P i E E P P GDP + P i GTP E P
Termination occurs when a stop codon in the mrn reaches the site of the ribosome The site accepts a protein called a release factor The release factor causes the addition of a water molecule instead of an amino acid This reaction releases the polypeptide, and the translation assembly then comes apart
Release factor Free polypeptide 2 GTP Stop codon (UG, U, or UG) 2 GDP + 2 P i
Often translation is not sufficient to make a functional protein During and after synthesis, a polypeptide chain spontaneously coils and folds into its three-dimensional shape Proteins may also require posttranslational modifications before doing their job
Two populations of ribosomes are evident in cells: free ribosomes (in the cytosol) and bound ribosomes (attached to the ER) Free ribosomes mostly synthesize proteins that function in the cytosol Bound ribosomes make proteins of the endomembrane system and proteins that are secreted from the cell Ribosomes are identical and can switch from free to bound
Polypeptide synthesis always begins in the cytosol Synthesis finishes in the cytosol unless the polypeptide signals the ribosome to attach to the ER Polypeptides destined for the ER or for secretion are marked by a signal peptide Ribosome mrn SRP Signal peptide Signal peptide removed ER membrane Protein ER LUMEN SRP receptor protein Translocation complex CYTOSOL
Mutations are changes in the genetic material of a cell or virus The change of a single nucleotide in a DN template strand can lead to the production of an abnormal protein
Point mutations are chemical changes in just one base pair of a gene Point mutations within a gene can be divided into two general categories Nucleotide-pair substitutions One or more nucleotide-pair insertions or deletions
Wild-type hemoglobin Sickle-cell hemoglobin Wild-type hemoglobin DN Mutant hemoglobin DN C T T C T G G T mrn G mrn G U Normal hemoglobin Glu Sickle-cell hemoglobin Val
nucleotide-pair substitution replaces one nucleotide and its partner with another pair of nucleotides Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code Missense mutations still code for an amino acid, but not the correct amino acid Nonsense mutations change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein
Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code Wild type DN template strand T C T T C C C G T T T G G T T T G G C T mrn Protein mino end U G G U U U G G C U Met Lys Phe Gly Stop Carboxyl end (a) Nucleotide-pair substitution: silent instead of G T C T T C C C T T T G G T T T G G T T U instead of C U G G U U U G G U U Met Lys Phe Gly Stop
Missense mutations still code for an amino acid, but not the correct amino acid Wild type DN template strand T C T T C C C G T T T G G T T T G G C T mrn Protein mino end U G G U U U G G C U Met Lys Phe Gly Stop Carboxyl end (a) Nucleotide-pair substitution: missense T instead of C T C T T C T C G T T T G G T T T G C T instead of G U G G U U U G C U Met Lys Phe Ser Stop
Nonsense mutations change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein Wild type DN template strand T C T T C C C G T T T G G T T T G G C T mrn Protein mino end U G G U U U G G C U Met Lys Phe Gly Stop Carboxyl end (a) Nucleotide-pair substitution: nonsense instead of T T instead of C T C T C C C G T T T G T G T T T G G C T U instead of U G U G U U U G G C U Met Stop
Insertions and deletions are additions or losses of nucleotide pairs in a gene These mutations have a disastrous effect on the resulting protein more often than substitutions do Insertion or deletion of nucleotides may alter the reading frame, producing a frameshift mutation
Wild type DN template strand T C T T C C C G T T T G G T T T G G C T mrn Protein mino end U G G U U U G G C U Met Lys Phe Gly Stop Carboxyl end (b) Nucleotide-pair insertion or deletion: frameshift causing immediate nonsense Extra T C T T C C G G T T T G T G T T T G G C T Extra U U G U G U U U G G C U Met Stop 1 nucleotide-pair insertion
Wild type DN template strand T C T T C C C G T T T G G T T T G G C T mrn Protein mino end U G G U U U G G C U Met Lys Phe Gly Stop Carboxyl end (b) Nucleotide-pair insertion or deletion: frameshift causing extensive missense missing T C T T C C C G T T T G G T T G G C T U missing U G G U U G G C U Met Lys Leu la 1 nucleotide-pair deletion
Wild type DN template strand T C T T C C C G T T T G G T T T G G C T mrn Protein mino end U G G U U U G G C U Met Lys Phe Gly Stop Carboxyl end (b) Nucleotide-pair insertion or deletion: no frameshift, but one amino acid missing T T C missing T C C C G T T T G T T T G G C T G missing U G U U U G G C U Met Phe Gly 3 nucleotide-pair deletion Stop
Spontaneous mutations can occur during DN replication, recombination, or repair Mutagens are physical or chemical agents that can cause mutations Carcinogen: causes cancer
Transcription and Translation Transcription nimation (more links on left) Translation Triplet Code Chargaff s Ratio