Translation

Question 1

formylmethionine

Answer 1

in bacterial protein synthesis, Initiator tRNA brings along N-formyl-methionine (fMet).
Synthesis begins at codon AUG
Ribosome binds at a conserved 5’ untranslated region (UTR) 10 bases upstream of AUG
Shine-Dalgarno sequence (AGGAGGU).

One of the ways for immune cells to distinguish self from pathogens is the presence of formylmethionine containing peptides.
These peptides are potent chemoattractants for neutrophils

Question 2

bacterial inhibitors of protein synthesis

Answer 2

Chloramphenicol:
inhibits peptidyl transferase in prokaryotes (50S).
Streptomycin:
Inhibits initiation to elongation transition (30S).
Erythromycin:
Inhibits translocation by binding to 50S ribosome.
Tetracycline:
prevents aminoacyl-tRNA binding to A site (30S).

Question 3

Hereditary thrombocythemia

Answer 3

Thrombopoietin (TPO):
It is produced in relatively low amounts in normal cells
It is a ligand for c-Mpl receptor
It regulates the production of platelets

Hereditary thrombocythemia:
Autosomal dominant disorder
Also known as familial thrombocytosis or familial essential thrombocythemia (FEH) 
High levels of TPO
Active proliferation of megakaryocytes
High platelet counts

Excess production of TPO is attributed to:
Mutations in TPO gene that restructure 5’ sequence in the mRNA.
Restructuring of leader sequence leads to efficient translation initiation at actual AUG start codon

Normal mRNA has several AUG codons, but functional full-length protein can
only be produced from AUG #8; AUG#7 and AUG#8 are overlapping–> low TPO because of the overlap doesn’t allow for the reinitiation at site #8.

in hereditary thrombocythemia, AUG#7 is eliminated by mutations and AUG#8 no longer overlap so the translation is read at AUG#8 nad translation becomes efficient–> more TPO

Question 4

Mdm2 Protein

Answer 4

Mdm2 is an oncogene because it accelerates degradation of p53, a tumor suppressor protein.

Mdm2 mRNA is inefficiently translated because of two AUGs upstream of the actual start codon.
In tumor cells, activation of a downstream promoter eliminates upstream AUGs making translation more efficient

Question 5

Alzheimer’s disease

Answer 5

Proteins may fold into an alternative 3-dimensional structure due to mutations and post-translational modifications.
Misfolded proteins are degraded by proteolysis
Proteolytic fragments aggregate and cause degenerative diseases.
Amyloid precursor protein (APP) is cleaved into A(beta)42 product that accumulates in Alzheimers

cleavage of APP by either alpha or beta secretase

with gamma secretase cleavage, get the toxic form.