Functions/Dysfunctions of Protein Processing Flashcards
TOM
Translocation sequences are recognized by Transporters in the Outer Membrane (TOM
TIM
translocation sequences are recognized by Transporters in the Inner Membrane (TIM)
Translocation complexes allow
signal protein to be passed through the inner and outer mitochondrial membrane
silent mutation
no change to the amino acid
missense mutation
changes amino acid in the protein with either no effect in function or a VERY different function
nonsense mutation
codon changes into a stop codon causing premature stop. Protein either degraded or truncated
Frameshift Mutation
one or more nucleotides deleted or inserted into ORF. OOF mutation changes codon/amino acid (DMD)
Sickle Cell Anemia
missense mutation of HBB
changes GAG to GTG-glutamate (hydrophilic) to valine (hydrophobic)
causes HbA to aggregate, make rod structures
deforms RBCs, sickle shape.
poor O2 capacity, clog capillaries and restrict blood supply
DMD
frameshift mutation (OOF) deletions in the dystrophin gene
little to no expression of dystrophin
muscle wasting
if an IFM occurs, results in truncated dystrophin causing milder BMD
Cytoplasmic Pathway
protein goes to cytosol, mitochondira, nucleus, perioxisomes
protein synthesis begins and ends on free ribosomes
Secretory Pathway
protein goes to ER, lysosomes, plasma membranes, secretion
translation starts on free ribosomes, ends on ribsomes that are sent to the ER
Proteins destined for ER lumen us the signal
C-terminal KDEL retention signal (lysine, aspartic acid, glutamic acid, leucine)
proteins destined for the lysosomes use the signal
mannose 6 phoshate
. DEFECT is I cell disease
proteins destined for secretion use the signal
tryptophan rich domain
proteins destined for secretion in membranes use the signal
N terminal nonpolar (GAPVIL M/W/F)
stop transfer sequence
Nuclear import occurs via
localization signals for larger proteins. signals consist of Lys Arg repeats (4) (KAKA)
Overview of secretory pathway
each protein has an ER targeting signal peptide 15-60 AA at the N terminus
1-2 basic AA (KA) near N terminus or hydrophobic sequence on C terminus of the basic residues
Signal recognition particle wraps around ribosome-mRNA -peptide complex tying it to ER membrane and stopping translation
Enzymes will cleave the signal to release the protein which can then continue on its journey
I cell disease
tagging of lysosomal proteins with manose 6 phosphate is defective
proteins not sent to lysosomes
high plasma levels of lysosomes
FTT, developmental delays, death.
Chaperones
help large proteins fold into 3’ state
Chaperonins
barrel shaped compartments that admit unfolded proteins and catalyze folding in ATP dependent manner.
Proteolytic cleavage
converts inactive forms to active enzymes by unmasking active site
converts nascent precursor proteins to mature ones (proinsulin to insulin)
O-glycocidic (glycocylation)
O-links are formed with OH groups of Ser, Thre
N-glycosidic linkage (glycosylation)
N-links are formed always with Aspargine transferred from phospho Dolichol
Phosphorylation forms
ester bond between P and OH of AA using Ser/Tyr kinase on Ser, Tyr, Thr, Asp, His
P removed via phsophatases
regualtes enzyme activity and function as well as cell growth, proliferation, oncogenes
