Post-Translocational Modifications Flashcards
What is a proteolytic cleavage?
Breaking peptide bonds to remove part of a protein - to make the protein inactive or to unsure it fold properly.
What is chemical modification?
The addition of a functional group to amino acid residues.
Where are proteins originally synthesised?
On the ribosomes of the endoplasmic reticulum.
After synthesis on the ribosomes, where are some locations proteins travel to?
Cytoplasm
Nucleus
Peroxisomes
Mitochrondria
What four components are needed for protein sorting?
A signal - ‘take me to the…’ - like an address
A receptor - recognises the signal
A translocation machinery
Energy to transfer
What signal is used to send the proteins to the peroxisomes?
A peroxisomal targeting sequence (PTS)
This is serine - lysine - leucine (SKL)
Present on the C terminus
What receptor is used when sending proteins to the peroxisomes?
The receptor Pex5
This binds to the protein cargo in the cytoplasm
What translocational machinery to used to take proteins to the peroxisomes?
13 PEX proteins that make up the transport channel
They bind the Pex5-cargo complex (Receptor + protein + translocational machinery)
What energy is used when taking the proteins to the peroxisomes and what is it needed for?
ATP hydrolysis
Not needed for protein to get across receptor, but to recycle receptor.
The the various steps from ER to peroxisomes of a protein.
Peroxisomal targeting sequence (PTS) of serine - lysine - leucine (SKL) present on the C terminus signals to be taken to the peroxisomes.
The translocational machinery of 13 pex proteins bind with the protein ‘cargo’
The receptor Pex5 pulls away from the peroxisomal membrane and binds to the cargo.
Brings cargo to the peroxisomal surface, releasing cargo across the membrane.
ATP hydrolysis is sued to recycle the receptor, so it can bind to another cargo in the cytoplasm.
What is Zellweger syndrome?
Reduction is functioning peroxisomes, unable to break down fatty acids.
This accumulations of fats causes neural impairment.
What is Rhizomelic chondrodysplasia punctata?
A mutation in the peroxisomes means they cant break down plasmalogens (phospholipid).
Results in skeletal abnormalities and respiratory problems.
What three types of proteins are sent for secretion?
Extracellular proteins, membrane proteins, vesicular proteins.
What are two types of secretions in the cell? Example?
Constitutive - going all the time e.g. Collagen.
Regulated - when needed e.g. Endocrine, exocrine, neurocrine cells.
What signal is needed to send a protein for secretion?
An N terminal amino acid sequence 5-30 amino acids in length.
Unable to form an alpha helix which is removed after synthesis e.g. Preproinsulin and proinsulin
What receptor is used to send proteins to be secreted?
Signal particle Receptor
What translocational machinery to used to send proteins for secretion?
Signal recognition particle (SRP).
Composed of 6 proteins and short piece of RNA.
What is the mechanism of protein from ribsomes to the ER to be used as a secretion?
The signal recognition particle binds to the protein, recognising its amino acid signal.
Once attached to the protein, it brings it to the ER surface, binds to the SRP receptor and releases the protein inside.
The SRP is then released and the signal sequence on the protein is cleaved by a signal peptide.
Name some functions of the ER?
Insertion of proteins into membranes Specific proteolytic cleavage Glycosylation Formation of S-S bonds Hydroxylation Assembly of multisubunit proteins Proper folding of proteins
What is N-linked glycosylation and why is it important?
A sugar is added on an asparagine side group (reactions involves an amino group NH2)
This is key for correct protein folding and stability.
What is a disulphide / SS bond?
A bond between two cysteine residues
This determines the tertiary structure of the protein
Is misfolding cannot be correcting what two things will happen to the protein? Give a disease example for each.
Protein is returned to the cytosine for degradation e.g. Cystic Fibrosis, Alzheimars
Proteins accumulate to toxic levels in the ER e.g. Parkinson’s, Charcot-Marie-Tooth Syndrome
What are the five layers of the Golgi complex and their position?
From the ER going away from: Cis-Golgi network Cis Cisterna Medial Cisterna Trans Cisterna Trans Golgi network
What is O-linked glycosylation?
The attachment of a sugar to an -OH group - serine and theomine.
Occurs in the Golgi and is important in proteoglycans to produce extracellular matrix and mucus secretions.
How does preproinsulin get to its ‘insulin’ form?
Before entry into the ER, the signal peptide of preproinsulin is cleaved to create proinsulin.
In the ER, disulphide (S-S) bonds are formed and the B chain is cleaved off to create insulin, which then enters the Golgi.
Why is proteolytic processing complex?
Because there are different amounts of processing enzymes in different cell locations.
