Lecture 2: Protein Processing Flashcards
What does streptomycin inhibit?
Binds to 30s subunit and interferes with binding of fmet-tRNA
-Impairs initiation
What doe clindamycin and erythromycin inhibit?
Binds to 50s subunit
-blocks translocation of ribosome
What does tetracycline inhibit?
Binds to 30s subunit and blocks entry of aminoacyl-tRNA to ribosomal complex
-impairs elongation
What does chloramphenicol inhibit?
Inhibits peptidyl transferase activity and impairs peptide bond formation in prokaryotes
How do Shiga toxin and ricin work?
Binds to 60s subunit and blocks entry of aminoacyl-tRNA to ribosomal complex
How does Diphtheria toxin work?
Inactivates GTP-bound elongation factor-2
-Impairs ribosomal translocation
How does cycloheximide work?
Inhibits peptidyl transferase activity and impairs peptide bond formation in eukaryotes
How does puromycin work?
Premature chain termination in both prokaryotes and eukaryotes
What is the pathology behind Sickle Cell Disease?
Missense mutation
Glutamic Acid –> Valine
What is the pathology behind Duchenne Muscular Dystrophy?
Frameshift mutation that leads to dysfunctional dystrophin protein in males
*muscle wasting
In the cytoplasmic pathway, where are proteins destined for?
Cytoplasm
Mitochondria
Nucleus
Peroxisomes
In the secretory pathway, where are proteins destined for?
Plasma Membrane
Lysosomes
Endoplasmic Reticulum
They have ER targeting signal peptide and undergo post-translational modification in ER/Golgi
What is the signal for a protein sent to the cytoplasm?
None
What is the signal for a protein sent to the mitochondria?
N-terminal hydrophobic alpha helix signal peptide
-recognized by TIM and TOM transporters in mitochondria
What is the signal for a protein sent to the nucleus?
KKKRK signal (lysine/arginine rich)
- imported via nuclear pores
- large proteins require nuclear localization signals
What is the signal for a protein sent to peroxisomes?
C-terminal SKL signal sequence
What is the signal for a protein sent to the ER Lumen?
C-terminal KDEL retention signal
What is the signal for a protein sent to the lysosomes?
Mannose 6-phosphate signal group
What is the signal for a protein sent out for secretion?
Tryptophan rich domain
What is the signal for a protein sent to the membranes?
N-terminal apolar region (stop transfer sequence)
What is glycosylation?
Proteins are covalently linked to sugar residue in ER lumen
O-glycosides: Hydroxyl groups on Ser or Thr residues
N-glycosides: Acid-amide group on Asparagine
What is phosphorylation?
Formation of ester bond between phosphate and OH group of amino acid
-Ser/Thr Activity or Tyrosine Kinase
What are disulfide bond formations?
Disulfide bonds stabilize proteins
Bonds between Thiol (SH) groups of 2 cysteine residues
Formation in ER lumen
Acetylation
Acetyl added on lysine residues
-important for protein modification
What is essential for the activity of lysyl and prolyl hydroxylases?
Ascorbic Acid
Defects in in lysyl hydroxylases can result in?
Skin, bone, joint disorders
- Ehlers-Danlos Syndrome
- Nevo Syndrome
- Bruck Syndrome
What is the pathology behind Alzheimer’s Disease?
Amyloid precursor protein breaks down to form Amyloid Beta Peptide (AB)
- misfolding and aggregation in brain
- Hyperphosphorylation of Tau
What is the pathology behind Parkinson’s Disease?
Aggregation of alpha-synuclein protein
- Deposits as Lewy bodies in dopaminergic neurons in substantia nigra
- Reduced availability of dopamine
What is the pathology behind Huntington’s Disease?
Mutation in huntingtin gene –> expansion in CAG triplets
-abnormal polyglutamine repeats
What is the pathology behind Creutzfeldt-Jakob Disease?
AKA Mad Cow Disease/Encephalopathy
- misfolding due to prion proteisn
- infection
- spongy brain
