Protein Targeting Flashcards
What is a signal sequence?
A short sequence of amino acids usually located on the N terminus on newly synthesised proteins that are destined for the secretory pathway
What is the Signal Recognition Particle?
Protein that recognises and targets specific proteins to the endoplasmic reticulum
What do chaperone proteins in the lumen of the ER do?
Help the polypeptide to fold correctly and protect the nascent polypeptide from interacting with other proteins
On which terminus is the signal sequence of proteins targeted to the ER located?
N terminus
Where is the signal sequence of proteins targeted to the nucleus located?
Various positions, must be on surface of folded protein
On which terminus is the signal sequence of proteins targeted to mitochondria located?
N terminus
On which terminus is the signal sequence of proteins destined for retention the ER located?
C terminus
Are proteins targeted to the ER folded or unfolded during transfer?
Unfolded - synthesised through membrane
Is the signal sequence in proteins destined for the ER cleaved or retained?
Cleaved by signal peptidase
Is energy required in protein targeting to the ER?
Yes - hydrolysis of GTP by SRP
What is an example of a protein retained in the ER?
PDI (protein disulphide isomerase)
What is the ER retention signal?
KDEL (Lysine-Aspartate-Glutamate-Leucine)
Are proteins retained in the ER folded or unfolded during transfer?
Folded - delivered via vesicle
Are proteins targeted to lysosomes folded or unfolded during transfer?
Folded - delivered via vesicle
Are proteins targeted to the nucleus folded or unfolded during transfer?
Folded - large pores in double membrane of nucleus
Are proteins targeted to the mitochondria folded or unfolded during transfer?
Held partially unfolded by chaperones (eg MSF)
Is the signal sequence in proteins destined for the nucleus cleaved or retained?
Retained - facilitates re-importing of proteins when nucleus reforms after cell division
Is the signal sequence in proteins destined for the mitochondria cleaved or retained?
Cleaved
Is the signal sequence in proteins destined for the lysosomes cleaved or retained?
Phosphate removed by phosphatase
Is the signal sequence in proteins retained in the ER cleaved or retained?
Retained
Is energy required in protein targeting to the nucleus?
Yes - hydrolysis of GTP
Is energy required in protein targeting to the mitochondria?
Yes - ATP hydrolysis by mHsp70 drives translocation; MSF uses ATP to keep some precursors unfolded
Is energy required in protein targeting to the lysosomes?
Yes - phosphotransferase ultimately requires ATP
Is energy required in protein targeting to remain in the ER?
No - involves binding and release dependent on pH
Briefly describe how proteins are targeted to the ER
- Signal sequence translated on N terminus of protein
- SRP binds to signal sequence
- Binding of SRP halts translation
- SRP receptors present on the membrane of ER
- SRP alongside signal sequence, polypeptide, mRNA and ribosome bind to SRP receptor on ER membrane
- SRP unbinds from signal sequence which binds to translocon
- Translation resumes
- Growing polypeptide ‘droops’ into lumen, where chaperone proteins associate with it and signal sequence is cleaved by signal peptidase
What specialist proteins are involved in protein targeting for proteins retained in ER?
KDEL receptor in cis-golgi
What specialist proteins are involved in protein targeting to ER?
SRP, SRP receptor
What specialist proteins are involved in protein targeting to nucleus?
Importin recognises NLS and mediates transport
RanGTP displaces it in nucleus and drives out export cargo
What specialist proteins are involved in protein targeting to mitochondria?
Mitochondrial-import stimulating factor (MSF)
Tom and Tim channel complex
What specialist proteins are involved in protein targeting to lysosomes?
M-6-P Receptor in trans golgi
