Protein Targeting Flashcards
What is protein targeting?
It answers the question: how do proteins, the functionality of the cell, move to different locations around the cell to define this functionality-
Locations include-organelles, membrane proteins, secreted proteins, cytosolic proteins
What structure of the proteins allows it to be directed to the correct location?
The primary - the sequence of amino acids in the protein
Describe 2 examples of proteins being targeted
targeting proteins to ER via signal peptide ( secreted proteins, membrane proteins, lysosomal proteins)
targeting cytosolic proteins to organelles via other peptide signals (Nuclear proteins, mitochondrial proteins, peroxisomal proteins)
Describe Protein synthesis in the ER
1) Protein synthesis starts with cytosolic ribosome
2) Signal sequence is first part of the protein synthesised ( N-terminus)
3) Signal sequence recognised by SRP protein complex
4) Signal sequence recognised by SRP receptor on the ER membrane- Ribosome now bound to the ER membrane
5) New protein is guided through translocation channel in the ER membrane into the ER lumen
6) Signal Sequence is cleaved via signal peptidase
SRP is recycled
Describe how Membrane proteins remain in the ER membrane
The Hydrophobic start transfer sequence is first part of the sequence to be translated and go through the transporter protein.
the hydrophobic stop transfer sequence goes through the transporter protein and remains embedded inside the membrane as a segment of proteins.
Simultaneously, the starts sequence is cleaved- by signal peptidase also found the membrane
Describe the movement of proteins from the ER to the Golgi
1) Protein synthesis is finished and folded in the ER and starts to be modified
2) These form vesicles that migrate and merge with cis Golgi
3) Further maturation occurs in the Golgi
4) Movement between the cisternae of the gills is via vesicles
5) By the trans membrane of the Golgi, protein is packaged into vesicles for specific compartments- via cytoskeleton pathway
a) integral membrane proteins
b) continous secretory pathway
c) Stimulated secretory pathway
d) formation of lysosome
How are vesicles targetted to specific compartments?
Vesicles have V snare
Target plasma membrane have t snare
The shape of these are complementary and specific to each other- facilitate the correct localisation
Snares dock
allowing membranes to fuse
How are proteins targeted to the mitochondria
This occurs after translation is completed- before the complete protein folding occurs
The protein is then complexed with a chaperone (HSP70)
1) Folded protein present in the cytosol- has the specific signal sequence
2) Signal sequence recognised by receptor like proteins on the plasma membrane of the mitochondrion
3) Process allows the mature protein to cross the mitochondrial membrane (translator- active)
4) Signal sequence is cleaved off- this is good because because it won’t be able to leave the mitochondria if it doesn’t have the signal protein
How are proteins targeted to the nucleus
1) Translation occurs after translation and folding has occurred in the cytosol
2) Nuclear proteins contains a NLS- it is short and basic
Pro-Lys-Lys-Arg-Lys-Val
Basic due to the NH2
3) NLS binds to importin (forming a complex) and is transported through a nuclear pore
This requires GTP hydrolysis and a G-protein
The complex then dissociates
Exportin performs the the reverse function exporting proteins from the nucleus
How are proteins targeted to lysosome
Lysosomal proteins are tagged with mannose-6-phosphate in Golgi
Mannose-6-phosphate receptor is on golgi membrane e
It directs the proteins to transport proteins
Vesicles are then converted to lysosome
Describe a example of portion targeting disorder inclusion cell disease
Mutant N-acteylglucosamine-1-phosphotransferase enzyme
phosphorylates mannose
therefore proteins involved in lysosomes not tagged with mannose-6-phosphate in golgi
Enzymes are secreted instead-
lysosomes do not function properly
Affects all tissues
Developmental defects
