BCHM2072/2972 Semester 2, 2004
PART A
55.
56.
Which of the following statements about protein folding in the ER is correct?
A.
The hydrophobic signal peptide is buried in the core of the protein as it folds.
FALSE The signal peptide is indeed hydrophobic, but it is not buried in the protein.
Instead it is cleaved by Signal Peptidase before folding.
B.
The reducing environment inside the ER ensures rapid formation of disulfide bonds in
proteins undergoing folding.
FALSE The environment inside the ER is oxidising, which facilitates the formation of
disulfide bonds. I’m sure you all know this, as it was in the assignment!
C.
Peptidyl disulfide isomerase forms covalent bonds with substrate proteins.
TRUE
D.
ATP hydrolysis catalysed by the signal recognition particle is used to drive protein
folding.
FALSE ATP hydrolysis is used for many things, but this isn’t one of them. The Signal
Recognition Particle recognises and binds to the signal peptide of the growing
polypeptide and draws the ribosome onto the ER by binding to the SRP receptor.
E.
UDP:glucosyl transferase removes glucose residues from glycoproteins which have
folded correctly.
FALSE UDP:glucosyl transferase adds glucose residues to glycoproteins, but only if
they are unfolded or incorrectly folded.
During biosynthesis of glycosylphosphatidylinositol (GPI) -anchored proteins:
A.
The GPI anchor becomes covalently linked to the S atom of a cysteine residue on the
protein.
FALSE See E.
B.
Dolichol phosphate is displaced by the GPI anchor in a transesterification reaction.
FALSE Dolichol phosphate is embedded in the ER and is a carrier of oligosaccharides,
not GPI.
C.
Inositol triphosphate is released and then acts to mobilise Ca2+ from intra-cellular
stores.
FALSE This doesn’t occur during the biosynthesis of GPI-anchored proteins, but
rather from the action of Phospholipase C.
D.
Glucose residues are trimmed from the GPI anchor.
FALSE GPI anchors contain glucosamine, not glucose. Glucose residues are trimmed
from glycosylated proteins.
BCHM2072/2972 Semester 2, 2004
E.
57.
58.
The GPI anchor is linked to the C-terminal of the protein in a transamidation
reaction.
TRUE
A common structural theme in the cytokine family of receptors is:
A.
They all contain seven strands of beta-sheet which span the cell membrane.
FALSE Even 7-TMS receptors only have α-helices.
B.
They all mediate signal transduction through G-protein coupled events.
FALSE This occurs with G protein-coupled receptors.
C.
Their extra-cellular domains are alpha-helical bundles.
FALSE No, they aren’t.
D.
They are all GPI-anchored proteins.
FALSE Again, no they aren’t.
E.
Typically, binding of cytokines to their receptors leads to dissociation of the receptors
into their active monomeric forms.
FALSE Cytokine binding leads to dimerisation or receptors.
(F.
None of the above.
TRUE Yes…, I know. I hope you didn’t spend hours on this one. I even checked with
Simon, and he agrees they are ALL wrong.)
Binding of a cytokine to a cytokine receptor would be generally expected to lead to:
A.
An influx of Ca2+ through activation of a ligand-gated ion channel.
FALSE This is typically achieved by the action of IP3 which in turn is released by the
action of Phospholipase C after binding of a signal molecule to a G protein-coupled
receptor or a receptor protein-tyrosine kinase.
B.
Translocation of the receptor:cytokine complex to the nucleus.
FALSE This only applies to steriod receptors.
C.
Autophosphorylation of a tyrosine kinase bound to the receptor.
TRUE Another one from the assignment (although ‘non-receptor protein-tyrosine
kinase associated with’ might be better than ‘tyrosine kinase bound to’).
D.
Dissociation of the receptor from a dimer to a monomer form.
FALSE Actually the opposite occurs.
E.
Inhibition of intra-cellular adenyl cyclase.
FALSE Adenyl cyclase is linked to G protein-coupled receptors via various
G proteins.
BCHM2072/2972 Semester 2, 2004
59.
60.
61.
Which of the following statements about the JAK-STAT signalling pathway is correct?
A.
Dephosphorylation of a JAK kinase allows the binding of a STAT transcription factor,
mediated by its SH2 domains.
FALSE It is phosphorylation that has this effect because SH2 domains bind
phospho-tyrosine residues.
B.
JAK kinases use GTP to phosphorylate small GTP-binding proteins such as Ras.
FALSE No, they don’t. Ras et al are involved with G protein-coupled receptors. See
60B.
C.
Phosphorylation of STAT proteins allows them to dimerise through their SH2
domains.
TRUE
D.
JAK-dependent phosphorylation of calmodulin leads to inhibition of Ca2+dependent protein kinases.
FALSE JAKs don’t phosphorylate calmodulin.
E.
Entry of JAK kinases to the nucleus is followed by phosphorylation of the 2’ OH
groups of the deoxyribose residues of chromosomal DNA.
FALSE STAT protein dimers enter the nucleus.
In general, binding of growth factors to receptors with intra-cellular tyrosine kinase domains
might be expected to:
A.
Lead to tyrosine kinase-catalysed dephosphorylation of phosphoproteins.
FALSE The whole point of kinases is that they phosphorylate other proteins.
B.
Lead to activation of the Ras protein kinase through the action of the Raf adaptor
protein.
FALSE After Grb2 (through its SH2 domain) has bound to the phosphotyrosine
sequence on the receptor, and Sos has bound to it, Ras is activated by Sos which is a
guanine nucleotide exchange factor (ie GDP GTP). The activation of Ras allows the
binding of Raf.
C.
Lead to the activation of protein kinase C because of decreased levels of intracellular Ca2+.
FALSE PKC is activated by increased levels of Ca2+.
D.
Culminate in the phosphorylation of transcription factors by a MAP kinase.
TRUE
E.
Lead to enhanced expression of protein kinase A.
FALSE PKA is involved with G protein-coupled receptors.
As a check on the scanning procedure enter an answer of A to question 61 on the answer sheet.
BCHM2072/2972 Semester 2, 2004
62.
63.
During activation of protein kinase C:
A.
An influx of Ca2+ from the nucleus to the cytoplasm leads to conversion of protein
kinase C into its active form.
FALSE The Ca2+ comes from the ER. See B
B.
Production of IP3 leads to the opening of a ligand-gated ion channel in the membrane
of the endoplasmic reticulum.
TRUE
C.
Protein kinase C enters the nucleus after a steroid hormone binds to it.
FALSE PKC is not a steriod receptor and does not bind steriod hormones, much less
translocate to the nucleus.
D.
Calmodulin-activated protein kinase binds to the IP3 receptor through its SH2
domain.
FALSE Ca2+ binding to calmodulin leads to it binding, and activating, PKs.
E.
Diacyl glycerol is phosphorylated and becomes incorporated into the cell membrane.
FALSE DAG is there already. It remains unphosphorylated and activates PKC
(together with Ca2+).
One of the characteristic features of G-protein coupled receptors is:
A.
Their primary role is signal transduction within cells of the immune system.
FALSE There are many 100s of these receptors and they have very diverse functions.
Some include: neurotransmission, sight, smell and taste.
B.
Normally, small GTP-binding proteins like Ras bind to G-protein coupled receptors
during their activation.
FALSE See 60B. Ras binds to Sos and GTP/GDP, not the receptor directly.
C.
G-protein coupled receptors are heterotrimers of alpha-, beta- and gamma-chains.
FALSE Be careful here – these receptors are associated with other molecules:
heterotrimeric G-proteins.
D.
In most cases, their monomeric forms are inactive.
FALSE This is one case where dimerisation is irrelevant. These receptors undergo a
structural change upon a ligand binding.
E.
They contain seven membrane-spanning alpha-helices.
TRUE Well, their other name IS ‘7-TMS receptors’.
PS. As you can see from the above, the devil is in the detail! Good luck all.