Lecture 6 Flashcards
Ribosomes remain cytosolic if the protein is…
destined for the cytosol or posttranslational import into organelles
ribosomes attach to ER membrane if protein…
destined for membrane or secretory pathway via co translational insertion
What is required for protein sorting?
a signal intrinsic to the protein
a receptor that recognizes the signal and which directs it to the correct membrane
a translocation machinery
energy transfer the protein to the new location
protein import into the mitochondrial matrix
1.protein with signal kept unfolded by chaperones
2.signal binds receptor
3.protein fed through channel in adjacent inner membrane
4/ targeting signal cleave
what is Pyruvate dehydrogenase deficiency
a mutation at codon 10 in N-MTS of PDH E1a subunit results in Arg to Pro substitution
Reduced uptake into mitochondria
X linked dominant disorder
The classic nuclear import cycle
Example of a mutation of the nuclear localisation signals
Swyer Syndrome
What is Swyer Syndrome?
loss or mutation of NLS determining SRY protein
XY genotype
outwardly female
SRY required for testis differentiation
Functions of the ER
insertion of proteins into membranes
specific proteolytic cleavage
glycosylation
formation of S bonds
proper folding of proteins
assembly of multiunit proteins
hydroxylation of selected Lys and Pro residues
What is Glycosylation
most common posttranslational modification
most of the secreted proteins become glycosylated
occurs in ER
further sugar modification takes place in the ER and golgi
Oligosaccharide preassembled on lipid
(dolichol) carrier
N linked Glycosylation -
sugars are added on an asparagine side chain (involves an amino group hence N linked)
O linked glycoslyation
sugar moiety added to serine or threonine
Why is glycosylation of proteins so important?
correct protein folding
protein stability
facilitates interactions with other molecules
deficiencies in N linked glycosylation lead to severe inherited human disease: congenital disorders of glycoslation
Delivery of lysosomal enzymes to the lysosome requires what kind of signal
mannose 6 phosphate signal
What enzymes are required in the delivery of lysosomal enzymes to the lysosome
N-acetyl glucosamine phosphotransferase and phosphodiesterase
As a lysosomal enzyme passes through the Golgi apparatus…
a phosphate group is added to the hydroxyl group of carbon 6
of a mannose sugar
O-linked glycoslation details:
occurs in Golgi
attachment of sugar to hydroxyl group of serine, threonine
important in proteoglycans
component of extracellular matrix and mucus secretions
Disulphide bond formation
occurs in the ER
between 2 cysteine amino acids
Redox reaction with a protein disulphide isomerase (PDI - an ER protein)
C-terminal KDEL motif - signal to return them to the ER
(KDEL = retrieval pathway)
how do proteins normally fold and what proteins can assist them?
many proteins fold into correct conformation but some need chaperone proteins to help them
What 3 things can happen when there are protein folding problems?
Protein may be trapped in mis-folded conformation
Protein contains mutation resulting in mis-folding
Protein may be incorrectly associated with other sub-units
BiP (chaperone protein)
binding immunoglobin protein
What does BiP do?
binds to exposed amino acid sequences that would normally be buried in the
interior of a folded protein
