Genetics Flashcards
Genetic Code
‘rules’ that convert the nucleotide sequence of a gene to a sequence of amino acids of a protein using mRNA as an intermediary
Degenerate Code
some amino acids can be coded by more than one codon and 3 codons are STOP codons
Silent Mutation
doesn’t change the amino acid
Missense Mutation
Changes amino acid in the protein with no effect on protein function
Nonsense Mutation
Codon changes to a stop codon
- causing premature chain termination
- protein is formed as a truncated version
- Protein is non-functional
Frameshift Mutation
One or more nucleotides are depleted or inserted into ORF, which causes a change in the codon sequence and a change in the amino acid sequence
*Protein is non-functional
Sickle Cell Anemia
missense mutation
- changes Val (hydrophobic) to Glu (-charged+hydrophil)
- changes in conformation of HbA: aggregate, rigid, rod-like structures
- deformed RBCs with poor oxygenation and clogs capillaries
Duchenne Muscular Dystrophy
- deletion in the dystrophin gene leading to partial or non-functional dystrophin protein
- OOF deletions give little/no expression of dystrophin protein
- muscle wasting
- frame shift deletions–truncated forms of dystrophin
mRNA
- 5’ cap
- -untranslated region
- -Coding region
- -3’untranslated region
- Poly A tails
tRNA
- serves as adaptors
- binding site for codons and amino acids
- match amino acids to codons in mRNA
- Clover leaf (2dry structure)
- Anticodon loop
- 3’CCA terminal region
3’ CCA terminal region
found in tRNA
-binds the amino acid that matches the corresponding codon
Anticodon loop
found in tRNA
-set of three consecutive nucleotides that pair with a complementary codon in mRNA
Aminoacyl tRNAs
(tRNA with amino acid)
- AA needs to be activated
- catalyzed by aminoacyl tRNA synthetases which serves as a second genetic code
- each tRNA is charged with the correct AA to maintain fidelity of protein synthesis
Activation of Amino Acids
- Aminoacyl tRNA synthetase catalyzes the addition of AMP to the carboxy end of AA
- the AA is transferred to the cognate tRNA
Ribosomes
assemblers of translational machinery
- large complexes of proteins and rRNA (L+S subunit)
- antibiotics are used to target prokaryotic translational machinery
Ribosomal Complex
- Acceptor site
- Peptidyl site
- Empty/Exit site
Acceptor Site
(on ribosome)
-mRNA codon exposed to receive aminoacyl tRNA
Peptidyl Site
(on ribosome)
-where aminoacyl tRNA is attached
Empty/Exit Site
(on ribosome)
-location occupied by empty tRNA before exiting the ribosome
Translation
5’ to 3’
- Initiation
- Elongation
- Termination
Initiation
(translation)
formation of mRNA, which is a small ribosomal subunit and initiator tRNA pre-initiation complex
-requires the hydrolysis of 1 GTP
Elongation
(translation)
-activated AA attached to initiating Methionine by forming a peptide bond
*requires the hydrolysis of 2 GTP per amino acid added
Termination
(translation)
- peptide chain is released from ribosomal complex
- requires hydrolysis of 1 GTP
Peptidyl transferase
(translation)
- catalyzes peptide bond formation between amino acid in A and P site
5’ cap
mRNA
-7 methyl guanasine cap
Streptomycin
binds 30s subunit to disrupt initiation of translation
Shigatoxin
binds to 60s subunit to disrupt elongation
Clindamycin/Erythromycin
bind 50s subunit to disrupt translocation of ribosome
Tetracyclines
bind 30s subunit to disrupt elongation
Peptidyl Transferase
housed in the large subunits of the ribosome
Diptheria Toxin
inactivates EF2-GTP and inhibits elongation
Prokaryote Ribosome
50s subunit and 30s subunit
Eukaryotic Ribosome
60s subunit and 40s subunit
Mitochondria Proteins
contain an N terminal hyrophobic alpha helix
have TOM or TIM to signal for peptide import
Nucleus Proteins
Rich in Lysine and Arginine
Peroxisome Proteins
have an SKL sequence (cytosolic pathway)
Endoplasmic Reticulum Proteins
Secretory Pathway
- go to ER first
- have an ER ‘retention signal’ with amino terminus (positive charge)
KDEL
Endoplasmic Reticulum ER retention signal
Lysosomal Proteins
have a mannose 6 phosphate signal from secretory pathway…go to ER first
Secretory Proteins
have Tryptophan rich domains…from secretory pathway that hit the ER first
Heat Shock Proteins
protect the unfolded proteins that are entering the mitochondria via the TOM and or TIM
SRP
Signal Recognition Particle–brings together the ER membrane and the ribosome
I-Cell Disease
lysosomal storage disorder to the defective tagging of lysosomal proteins with Mannose-6-Phosphate so there is an increase is plasma lysosome levels
Chaperone Proteins
needed by large proteins for protection and folding guidance into proper tertiary structure to avoid aggregation and proteolysis
Chaperonins
barrel shaped compartments that admit unfolded proteins and catalyze folding in an ATP dependent manner
Glycosylation
PTM
- O linked form in a serine residue
- N linked form in Asparagine
*cataract formation
Post-Translational Modification of Collagen
Modification is important to collagen
Ascorbic acid is necessary for lysyl and proyxl hydroxylases and defects in this enzyme result in disorders such as Erlhers Danlos
