Post-translational modifications of proteins Flashcards
What is a conformer?
A protein that has been folded in different ways
Why do there tend to be amino acid variants?
Due to RNA editing of a single gene (different forms are encoded by a single gene)
What is the proteome?
It is the entire complement of proteins that is or can be expressed by a cell, tissue or organism
In order to get from a polypeptide chain to a functional protein, what must the protein do?
- fold into unique 3D shapes
- undergo modifications
- be sorted into its correct cellular location
- assemble correctly with other protein subunits with which it functions
The information for these proteins modification is ultimately contained within what?
the primary amino acid sequence
What are the 5 different post-translational modifications that proteins can undergo ?
- modification of amino acids
- modification during folding
- modification during transport
- modification required to activate proteins
- reversable modification that regulate protein activity (not covering here)
How many common amino acids are there?
There are 20 common amino acids
What are all the different types of modifications proteins can go through after its been produced?
What amino acids are most commonly phosphorylated?
Serine, Threonine, Tyrosine
What does the phosphorylation of the amino acids tend to change?
The charge of the R-group
What amino acid can mimic the switch permanently of phosphorylation and what amino acid can create an unswitchable version?
Aspartate mimics the switch permanently
alanine can create an unswitchable version
Give 3 other examples for how amino acids are modified, what they are modified by and then what the modified amino acids are used for ?
1. Conversion of glutamic acid to gamma-caboxyglutamate by vitament K-dependant carboxylase.
This is most commonly used in blood clotting protiens such as Prothrombin (its important because it binds platelets which helps to form clots)
2. Conversion of proline to 4-hydroxyproline in collagen and plant cell wall protein. This is done by enzyme 4-polyl hydroxylase
3. Conversion of lysine to 5-hydroxyline in collagen and 6-N-merthyl lysine in myosin (important for transcription and also structurally). This is done by lysyl hydroxylase enzymes
Whats an example of a reversable PTM?
What is it used in?
What does it help stop?
Lysine acetylation is an example of a reversable modification
It is used in transcription control
it also helps stop the interaction between DNA and the histone
Whats Ubiquitination? What terminus does it occur through?
an enzyme PTM in which a ubiquitin protein is attached to a substrate protein. This modification occurs through the C- terminus.
in Ubiquitination, whats the main function of the proteasome?
to degrade unneeded or damaged proteins by proteolysis
What can be used to anchor proteins to membranes?
Give 3 examples of this and where they are bound to on the amino acid?
fatty acids and lipids
examples:
1. Myristoylation (C14 fatty acid to N-terminal glycine)
2. Palmitoylation (C16 fatty acid to internal cysteine)
3. Prenylation (prenyl lipid to cysteins 4 residues from C-terminus)
Whats an important function of selenoproteins?
their antioxidant activity
What 2 enzyme promote the correct folding of a protein by catalysing modification reactions?
Give the name and what they catalyse
1. Peptidyl prolyl isomerase catalyses proline isomerisation. (proline tends to be in the cis posirtion but would work better in the trans position so this protein helps to change its conformation)
2. Protein disulphide isomerase promotes correct disulphide bond formation
Disulphide bond formation occurs through the reaction of the nearest thiol (-SH) group is not always desirable, name a protien that corrects this inappropriate disulphide bond formation during protein synthesis?
Protein disulphide isomerase
Whats the most common signal sequence? Give 2 examples of this and where the signals direct the proteins to?
The most common type of signal sequences is an N-terminal peptide
Examples include:
1. Signal peptide (SP) directing proteins to the ER
2. Transit proteins (TP) directing proteins to the chloroplast and the mitochondria
In some cases, there can be 2 signal sequences, where do these tend to direct proteins?
They initially direct proteins to the chloroplast and then intot he thylakoid lumen
What happens to signal sequences immediately after transport and what is this done by?
Signal sequences are cleaved immediately after transport is complete by a peptidase in the target compartment
Protein modifications are required to activate proteins. In what ways is this done (theres 3)
1. Proteolytic cleavage
2. Binding of cofactors
3. Assembly into oligomeric complexes (also important in folding)
Give 2 examples of protein modification through proteolytic cleavage?
1. pre-proinsulin –> insulin
Pre-proinsulin (no disulphide bridges) –ER–> proinsulin–Golgi–> insulin
(look up image in lecture 10)
2. Conversion of Zymogens to active enzymes
Zymogens are precursors of enzymes that are activated in a proteolytic cascade after release as granuels into the duodenum
