Post Translational Processing Of Proteins Flashcards
What is post-transitional modification?
Some proteins require additional processing after translation. This could be:
Proteolytic cleavage: breaking peptide bonds to remove part of the protein
Chemical modification: addition of functional groups to amino acid residues
How do proteins know where to go in the cell?
Proteins have intrinsic signals that govern their transport and localisation in the cell
Where are proteins destined for typos on or postranslational import into organelles synthesised?
Free ribosomes
Where are proteins destined for membrane or secretory pathway via co-translational insertion synthesised?
Ribosomes on the RER
Extruded into lumen of ER and then into golgi
What is required for protein sorting?
A signal intrinsic to the protein (so cell “knows” where to take the protein)
A receptor that recognises the signal and which directs it to the correct membrane
A translocation machinery
Energy to transfer the protein to its new place
What is needed for protein targeting to peroxisomes?
Signal: serine-lysine-leucine (SKL) - this is the peroxisome targeting sequence (PTS) - usually present on C terminus
Receptor - PTS receptor Pex5 - binds to the cargo protein in the cytoplasm
Translocation machinery - 13 pex proteins make up a transport channel across the peroxisomal membrane - binds to the Pex5-cargo complex
Energy - ATP hydrolysis to allow recycling of the PTS receptor
Describe the steps in targeting proteins to peroxisomes
- In cytosol peroxisomal import receptor binds cargo with PTS
- Peroxisomal protein remains folded and receptor integrates into translocon thereby opening it
- Peroxisome targeting sequence dissociates from receptor
- Receptor is returned to cytosol which requires ATP hydrolysis
What happens if targeting to peroxisomes goes wrong?
Peroxisome biogenesis disorders
e.g. Zellweger syndrome
Rhizomelic Chondrodysplasia Punctata
Briefly describe targeting proteins to the ER/secretory pathway (cotranslational transport)
Er is the main organelle which carries out process
As protein is made, it goes into ER
ER forms a continuum with Golgi
Bits of ER can bud off and go to Golgi
Insides are different though
ER buds across to cis Golgi
Trans Golgi is where secretory vesicles are released
What are the types of secretion from cells?
Constitutive secretion (happens all the time)
Regulated secretion (controlled - can switch it on and off)
Endocrine cells – secreting hormones
Exocrine cells – secreting digestive juices
Neurocrine cells – secreting neurotransmitters
What is a signal sequence?
N-terminal aa sequence
5- 30 amino acids in length
Central region rich in hydrophobic residues
Able to form a-helix
“Pre” defines signal sequence removed during processing
What is the SRP?
Signal recognition particle
Receptor needed to bind the signal peptide on proteins destined for the ER
Composed of 6 proteins and a short piece of RNA
Recognises the signal peptide and the ribosome
Describe the synthesis of secretory proteins and their translocation across the ER membrane
Secreted proteins start out on free ribosomes - mRNA start to be made here, start to produce n term
Gets recognised by SRP - binds - stops protein synthesis
This complex then binds to receptor on ER (SRP receptor)
Hydrolysis of GTP - energy - opens channel - SRP falls off
Ribosome docked
Protein synthesis starts again
N term enters lumen of ER, signal chopped off by signal peptidase
When finished ribosome dissociated
What is the purpose of a stop transfer sequence?
Halts the transfer of the peptide across the ER membrane - hydrophobic so anchors the protein in the membrane
What are the functions of the ER?
- Insertion of proteins into membranes
- Specific proteolytic cleavage
- Glycosylation
- Formation of S-S bonds
- Proper folding of proteins
- Assembly of multisubunit proteins
- Hydroxylation of selected Lys and Pro residues
