protein targeting and export 2 Flashcards
to the nucleolus
how does it go there and what is stopping it
not membrane bound
NOLS - nucleoar localisation signal
which is a longer version of NLS and has a run of basic residues K/R
going to mitochondria
what is needed and home much goes in
99% of mitochondrial proteins come from nuclear genome
mitochondrial matrix targeting what is it
what does it require
n terminal matrix targeting sequence
20-50 aa rich in hydrophobic aa +ve, and hydroxylated aa (s/t) forming amphipathic alpha helix
amphipathic alpha helix which has
+ve chare on one side
hydrophobic on other
mitochondrial targeting peptide mTP
what does it do
binds to receptor on mitochondrial outer surface and brought towards translocase of the outer membrane TOM
step 1 of translocation
unfolding helped by chaperones (HSC70) which requires ATP
step 2 of translocation
mTP binds to import receptor
step 3 of translocation
brings protein to TOM pore
step 4 of translocation
protein begins to pass through
step 5 of translocation
close proximity of TIM complex enables passage through inner membrane helped by ATP turnover by matrix HSC70
step 6 of translocation
mTP is removed by protease
step 7 of translocation
chaperones help refold protein to active state
what else foes the TIM pore/membrane do to help translocation
mitochondrial MP helps drive import via electrophorysis due to attraction of +vely charged AA in mTP towards matrix
dues to oxidative phosphorylation having high [h+] in the intermembrane space
leaky scanning what is it
isoforms of a protein with different N-termini can be produced by thus
if the sequence context surrounding the initiation codon is weak
alternate initiation
extended open reading frame eORF
translated from a non-AUG contains NLS
alternate initiation
annotated form aORF
translated from a weak AUG stays in cytosol
alternate initiation
shorter truncated form tORF
translated from a internal AUG
contains mTP
mitochondrial diseases
human deafness - dystonia syndrome
what causes it
what doesit cause
in recessive X-linked
leads to hearing loss, metal retardation and blindness
caused by mutation in TIMM8A
what does a mutation in TIMM8A do
moves proteins to intermembrane space
what does the mutation of TIM14 cause
autosomal recessive dilated cardio-myopathy with ataxia (DCMA) syndrome
what can the alpha-beta peptide do to the TOM TIM pores
plug them up
linked to Alzheimer
and inhibition of cytochrome C oxidase
