Post Translational Modifications Flashcards
What do ptms get added to
Proteins post translation
How is it possible there’s more proteins than mrna
Because of ptms
What is the definition of ptms
Covalent addition or cleavage to a terminal or aa chain
Ptms are said to add diversity to 21 aa, how
Additional of functional groups like phosphate, acetyl,methyl, carb,lipid
What are pluripotent stem cells and where they found
Stem cells (embryonic) which are taken from blastocyst and can differentiate into any type of cell
What 3 germ layers can pluripotent sc differentiate into
Ectoderm, mesoderm, endoderm
How are PTMs involved in pluripotency
Control direction and differentiation of the pluripotent sc
How can ptms be used to make induced psc
They can revert differentiated cells back via ptm of specific transcription factors
How are multipotent sc diff (adult sc Eg bone marrow)
Are limited into what type of cell they differentiate into
Are ptms reversible
Some are, some are irreversible
Give example of cleavage of proteins needed for activation (in er)
When some membrane proteins/secretory proteins produced on ribosomes in er, they enter the er and the signal peptide for localisation is cleaved by signal peptidases
Where other than er can more cleavage be done to activate proteins like insulin
Golgi transport after er
What is needed for insulin cleavage in Golgi for activation
Carboxypeptidase e (remove basic residues from c terminal) and proteases (also liberate c terminal)
This is after n terminal signal peptidase
When are functional groups added like ubiquitination,phos in PtMs
Only in response to signal like oxidative stress
What machine can detect ptms on proteins
Mass spectrometer
Is phosphorylation reversible ptm
Yes
How does phos both activate or deactivate
Can either mask bs/as on proteins or allow interaction with other proteins/molecules
How does protein kinase work
Atp hydrolysis to add a P to a hydroxyl end on a protein
The H from hydroxyl is removed (O) bond
What residues are usually phosphorylsted via their hydroxyl end
Serine, threonine, tyrosine
Which conserved domain do most kinases have which is homologous
Eukaryotic protein kinase domain
Is kinase activity favoured
Yes. Free energy when phosphate bond broken in atp
How do phosphatases work
Hydrolysis of the phosphoric acid monoester
Reforms atp
Add H back to hydroxyl group
Explain how glycogenolysis is a phosphorylation cascade
Epinephrine binding
Camp activated
Activated pka
Phosphorylates phosphorylase kinase
Phosphorylase kinase then phosphorylates glycogen phosphorylase = active to breakdown glycogen
How are monosaccharides added to hydroxyl groups on proteins in glycolysation
After production of monosaccharides they get added via glycosyltransferases, forming covalent glycosidic bond
Where does most glycosylation occur (N glycans in particular)
Inside the er after ribosome protein production
What is a core glycan made from
2 x gluNac (n acetyl glucosamine)
3x mannose
How many different monosaccharides can be added in glycosylation to how many aa
13
8 diff aa
What are some functions of glycosylation
Protein folding
Immunology (MHC are glycoproteins, ab)
Cell adhesion and interaction
Embryonic development
What helps oligosaccharides transfer to the protein hydroxyls in glycosylation
Dolichol
First type of glycosylation is N linked. Describe where and examples
Glycosylation on asparagine OH
In ER
Eg insulin receptors, extracellular matrix
What is O linked glycosylation
Glycosylation at OH of serine or threonine
Where does O linked glycosylation occur
Er, Golgi, cytosol and nucleus
Give examples of O linked
ECM, pathogenic toxins, collagen
Other than n and onlinked what are the other 3
Glypiation
C linked
Phosphoglycosylation
What is glypiation and give example
Core glycan (2 gluNac,3man) added to both phospholipid and protein
= in anchor cell surface proteins
What is c linked glycosylation
Mannose glycosylation
Binds to an Indole ring on tryptophan
Where is c linked glycosylation
Only in mammals
ECM
What is phosphoglycosylation
Glycan binds serine through a phosphodiester bond
Which ptm can be both co translational or post translation
Acetylation/deacetylation
What is acetylation related to via function
Gene expression
What are the 2 types of acetylation
N terminal (80-90%)
Lysine acetylation
What is n terminal acetylation
Acetyl added to amino group of first aa
Happens co translationally
Most proteins have n terminal acetylation (80%)
Which enzymes involved in n terminal acetylation which happens cotranslation
NATs
N terminal acetyl transferases
Give example of lysine acetylation
To control gene exp via chromatin remodelling. Lysine gets acetylated (HATs)
Also p53 residues get acetylated
Which enzymes are targeted for cancer therapeutics
HDACs
HDAC inhibitors are used to treat T cell lymphoma
What is the purpose of n terminal acetylation
Localisation and stability of proteins
Which residues get methylated (monomethyl,di or tri)
Lysine or arginine
Where is methyl donated to methylases from
S adenosylmethionine
Which type of methylation is reversible
Carbonyl methylation
Which methylation is irreversible
Nitrogen methylation
What is arginine methylation for
Rna processing and txn regulation
Dna damage repair
Protein translocation
What is lysine methylation for
Histone remodelling to control levels of expression
Epigentic regulation of txn
(Via HKMT)
What is p53 rich in which allows acetylation and methylation
Lysine and arginine
Why is acetylation advantageous of p53 via cbp /p300
It allows better access for p53 to dna makes nucleosomes less wrapped
