7. Precursor Processing Flashcards
5’ untranslated region (UTR)
area between the 5’ cap and the first coding exon
non-coding mRNA functions as?
regulators of protein translation
3’ UTR region
sequence between the last exon and the site of translation termination
translocation
proteins made in the cytoplasm, where they can remain or become targeted for movement to other organelles
the ribosomes targeted to the ER form proteins that will be?
membrane associated
have transmembrane domains
or are destined for secretion
what is the signal hypothesis?
states that certain sequences direct the ribosome to a translocator in the membrane of the ER, which forms a pore for translocation
the protein is processed by signal peptidases to cleave off the signal sequence, and the primary sequence dictates if the protein is a soluble or membrane protein
what is translocation directed by?
SRP (signal related peptide)
signal sequence is on the N terminal of the protein
when a polypeptide emerges from a ribosome, what does SRP do?
targets the ribosome to the translocator & binds to the SRP receptor & signal sequence
& tightly binds large ribosomal subunit to stop translation
hydropathy plot
used to determine the free energy of a reaction where a section of the protein leaves the membrane to enter an aqueous membrane
hydrophobic residues
high free energy
unfavorable
hydrophilic residues
low free energy/neg free energy
favorable
components of a signal peptide/leader sequence
12-36 AAs
significant sequence of basic amino acids
includes initiator methionine & at least 1 positively charged AA
cleavage site for signal peptidases preceded by residues with small R groups
when can protein folding occur?
once the polypeptide enters the ER
constitutive secretory pathway
unregulated; how many secretory & membrane proteins access the plasma membrane
regulated secretory pathway
tightly coupled to signaling cascades to secretory vesicles
when proteins leave the ER, where do they go?
to Golgi, then in vesicles to plasma membrane
C terminal modification
has amide group to protect against degradation by carboxypeptidases
N terminal modification
acetylated, diacetylated, pyrogluatml addition
glycine residue in peptides signals what?
amidation
3 enzymes that carry out protein precursor processing?
- proprotein convertase
- carboxypeptidase
- peptidyl-glycine a-mono-oxygenase
proprotein convertase (PC)
cuts on the C terminal end of basic AAs
carboxypeptidase (E)
chews off C terminal amino acids until it reaches glycine
peptidyl-glycine a-mono-oxygenase
cuts glycine in half, which leaves amide from the peptide bond
example of processing: POMC
processing of the same precursor in different tissues cn make various copies of different, biologically active proteins
what happens when the rate of protein synthesis is very fast?
ER can’t keep up in folding proteins, unfolded proteins begin to build up in the ER
what is activated when unfolded proteins build up in the ER?
PERK (pancreatic endoplasmic reticulum-resident kinase)
what does PERK do?
dimerizes & phosphorylates eIF2, inhibiting protein synthesis & allowing for ER to catch up with protein folding
if level of unfolded protein persists?
apoptosis
i. e. family who developed central D.I.
pt. mutation in vasopressin gene did not allow for proper precursor processing, which activated the unfolded protein response & induced apoptosis in the magnocellular neurons
