Functions and Dysfunctions of Protein Processing Flashcards
Streptomycin method of action
Binds to 30S subunit and interferes with binding of fmet-tRNA and impairs initiation. Interferes with 30S association with 50S
Clindamycin and erythromycin method of action
Binds to large 50S subunit, blocking translocation of the ribosome
Tetracycline method of action
Binds to small 30S subunit, blocks entry of aminoacyl-tRNA to ribosomal complex, impairs elongation
Chloramphenicol method of action
Inhibits peptidyl transferase activity and impairs peptide bond formation
Shiga toxin and ricin method of action
Binds to large 60S subunit (euk.), blocking entry of aminoacyl-tRNA to ribosomal complex
Diphtheria toxin method of action
Inactivates GTP bound EF-2, interfering with ribosomal translocation (euk.)
Cycloheximide method of action
Inhibits peptidyl transferase (euk.) and impairs peptide bond formation
Puromycin method of action
Enters A site and adds to the growing chain
Causes premature chain termination, stops the ribosome from functioning
What causes sickle cell anemia
Missense mutation changes GAG to GTG (glutamic acid to valine)
This alters conformation of HbA, causing it to aggregate and form rigid, rod like structures
What causes Duchenne muscular dystrophy
Large in frame and out of frame deletions to the dystrophin gene.
OOF deletions result in little/no expression of dystrophin
In frame deletions result in expression of truncated forms of dystrophin, giving rise to milder form of disease called Becker muscular dystrophy
Proteins bound for cytosol, mito, nucleus or peroxisomes are translated where
Free ribosomes in cytoplasm
Proteins destined for ER, lysosomes, plasma membrane or secretion are translated where
Translation begins on free ribosomes but terminates on ribosomes sent to ER. The proteins have ER targeting sequences present on the first 20 AA residues of the polypeptide
What does the nuclear localization signal consist of
Four continuous basic residues- lysine and arginine
Properties of secretory pathway ER-targeting signal peptide
1-2 basic AAs (lysine or arginine) near N terminus
Extremely hydrophobic sequence 10-15AAs long on C terminus
SRP binds to ER-targeting signal and ribosome
Translation is halted temporarily, resumed once protein is directed to ER lumen
AA signal sequence for ER lumen proteins
KDEL Lysine Aspartic acid Glutamic acid Leucine
Signal for lysosomal proteins
Mannose-6-phosphate
Signal for membrane proteins
N terminal apolar sequences
Signal for secretory proteins
Tryptophan rich domain
I-cell disease
Tagging of lysosomal proteins with M6P is defective
High plasma levels of lysosomal enzymes
Hepatosplenomegaly, recurrent respiratory inf., delayed motor and cognitive skills, abnormal skeletal development, death by 7
Which AAs may be modified by acetylation
Lysine
Which AAs may be modified by O-glycosylation (OH) and N-glycosylation (CONH2)
O- serine, threonine
N- Asparagine, glutamine
Which AAs may be modified by phosphorylation
Serine, tyrosine, threonine, aspartate, histidine
Which AAs may be modified by disulfide bond
Cysteine
Where in the cell are disulfide bonds added
ER lumen
Modifications to AAs in collagen include
Glycosylation and deamination of lysine
Hydroxylation of proline
Ascorbic acid and collagen
Ascorbic acid is essential for activity of lysyl and prolyl hydroxylases, which modify lysine and proline in collagen
Ehlers-Danlos syndrome
Defect in lysyl hydroxylase
Overly flexible joints; walls of blood vessels, intestines or uterus may rupture
Epidermolysis bullosa simplex
Defect in lysyl hydroxylase
Blisters on skin
Huntingtons disease
Loss of movement and cognitive functions and psychiatric problems
Crutzfeldt-Jacob disease
Failing memory, behavioral changes, lack of coordination and visual disturbances. Late stages involve mental deterioration, blindness, weakness of extremities and coma
What causes Alzheimers
Amyloid precursor protein APP breaks down to form amyloid beta peptide
Misfolding/aggregation of Ab forms plaques in brain (extracellular)
Hyperphosphorylation of Tau (neurofibrillary tangles) are intracellular
Mutations in APP and Tau cause familial forms of AD
What causes Parkinsons disease
Aggregation of a-synuclein (AS) protein forms insoluble fibrils which deposit as Lewy bodies in dopaminergic neurons in substantia niagra. Mutations in AS cause familial form of Parkinsons
What causes huntingtons disease
Mutation in Huntington gene results in expansion of CAG triplet repeats. Results in polyglutamine repeats in abnormal huntington protein. Forms intramolecular H-bonds, which eventually misfold and aggegate
-Death of cells in basal ganglia causes symptoms
What causes Creutzfeldt-Jakob disease
Caused by misfolding of prion proteins
Transmissible- infection by misfolded proteins converts normal proteins to misfolded
Belongs to Transmissible spongiform encephalopathies
Spongiform- appearance of infected brains, filled with holes and resembles sponges under a microscope
Don’t forget to look at videos for LOs 1&2 (Key components of protein synthesis and mechanism of translation)
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