Protein Processing Flashcards
In which 2 places can ribosomes be?
attached to RER or in cytosol
Where would the ribosome be if the protein being synthesised was destined for secretion or the membrane?
attached to RER
Where would the ribosome be if the protein being synthesised is destined for the cytosol or organelles?
In the cytosol
Where on the protein is the signal if it is destined to go to the ER?
N terminus
If destined for the ER, is the protein folded during transfer and what are the specialised proteins required?
No - it is unfolded during transfer
SRP - signal recognition protein
SRP receptor
Is the signal cleaved if destined for the ER?
Yes - by signal peptidase
Does protein transfer to the ER require energy?
Yes - GTP
What do we call the signal if the protein is destined for the nucleus?
NLS - nuclear localising signal
Where is the NLS found?
On the surface of the folded protein
What are the 2 important proteins for processing into the nucleus and what do they do?
Importin - recognises NLS and mediates transport
RanGTP - displaces importin in the nucleus
Is the signal cleaved in nuclear transport?
No - the signal is retained because it is needed in cell division
What kind of signal is required for mitochondrial transport and where is it located?
Amphipathic signal
N terminus
Is the protein folded during transport to the mitochondria?
No
It is held partially unfolded by a chaperone protein (MSF)
What does MSF stand for?
Mitochondrial-import stimulating factor
What specialist proteins are required for transport into the mitochondria?
MSF: chaperone protein
TOM: transport channel on outer membrane
TIM: transport channel on inner membrane
Is the signal cleaved during mitochondrial transfer?
Yes
Is energy required for mitochondrial transfer?
Yes - ATP
What is the signal for transport to lysosomes?
mannose-6-phosphate
Added post-translation
Is the protein folded during transfer to lysosomes?
Yes - it is delivered in a vesicle
Where is the M-6-P receptor?
Trans-Golgi
Is the signal removed after transport the lysosomes?
Yes - the phosphate is cleaved by phosphatase
Is energy required for transport to lysosomes?
Yes - ATP
What and where is the signal for retention in the ER?
KDEL signal
C terminus
What is constitutive secretion?
When something is being secreted all the time. It does not rely on stimulation.
Is the protein folded during retention in the ER?
Yes - it is transported via vesicle
What and where is the receptor for the KDEL signal?
KDEL receptor
Cis-Golgi
Is the signal cleaved for retention in the ER?
No - is required to keep the process going
Is energy required for retention in the ER?
No
Except a very small amount is required for the budding off of vesicles
How could someone have pyruvate dehydrogenase deficiency due to a fault in the protein processing?
If there is a mutation in the mitochondrial targeting sequence on pyruvate dehydrogenase then it cannot enter the mitochondria.
What is Swyer Syndrome?
The loss or mutation of NLS in the sex determining region of the Y protein.
You would be outwardly female as there is no testis differentiation.
What is the SHOX transcription factor required for?
Skeletal development
What are the functions of the ER?
insertion of proteins into membranes specific proteolytic cleavage glycosylation formation of disulfide bonds folding of proteins assembly of some multi subunit proteins hydroxylation of selected Lys and Pro residues
What is glycosylation important for?
correct folding, stability and interaction with other molecules
How does N-linked glycosylation work?
Sugars are added to an asparagine side chain.
What does the enzyme protein disulfide Isomerase do?
Forms disulfide bonds in the ER
How does O-linked glycosylation work?
Attachment of sugar to the -OH group of serine or threonine in the Golgi.
What is tropocollagen?
the basic unit of collagen
3 polypeptide alpha chains in a triple helix
Which 2 enzymes are important in collagen synthesis and what do they do?
Prolyl hydroxylase - hydroxylation of selected Pro and Lys residues
Lysyl oxidase - allows covalent cross-linking of collagen molecules to form fibres
Which enzyme requires vitamin C?
Prolyl hydroxylase
What is the simple sequence of events for collagen synthesis?
- Enters RER
- Cleavage of signal
- Hydroxylation
- N linked glycosylation
- Addition of galactose
- Disulfide bond formation
- Triple helix formation
- Addition of glucose
- Vesicle to exocytosis
- Terminal propeptide removal
- Covalent cross-linking
- Aggregation of fibrils to fibres
What are the 2 causes of Ehlers-Danos Syndrome? (Stretchy skin)
mutation in type III or V collagen
Lysyl oxidase deficiency
