L2: Post Translational Modification Flashcards
What happens in post translational modification (PTM)?
AA sequences is altered in terms of adding or removing aspects of the peptide, to change the way it folds
- thereby changing the final tertiary + quatermary structuring giving it different functions
When does PTM occur?
After protein biosyntheis on the aa chain or at a terminal
What are pluripotent stem cells?
Cells that can potentially differentiate into any cell in the human body
How does PTM affect the proteome?
It increase proteome diversity whilst extending functino and stability
Name the 5 common types of PTM
- phosphorylation
- methylation
- acetylation
- glycosylation
- disulfide bonds
What are the 4 methods of introducing new functional groups?
- phosphorylation
- glycolysation
- acetylation
- methylation
Explain how phosphorylation can be used to add new functional groups
Phosphate can be added or removed causing conformational change in protein, which can activate or deactivate an enzyme
What is phosphorylation
The adding of phosphate groups to the protein, therefore changing the electric nature of the aa
How does phosphorylation change the nature of an AA?
- changes bonding patterns, angles between adjacent AAs and interactions with other AAs
- thus changes the shape and structure and potentially its enzymatic processes
What are the possible outcomes of phopshorylation
- significant conformational change from the 2 -ve charges from the phosphate
- form a site recognised by other proteins
- can mask a binding site preventing protein- protein interaction
How can the transfer or removal of a phosphate group be catalysed?
- Protein kinases catalyse transfer using ATP
- Phosphates catalyse removal by hydrolysis. Can be specific or non, controlled by regulatory proteins
What is glcosylation?
When a carbohydrate is covalently bound to a functonal group, occuring in both euk and prokary cells
What are the functions of glycosylation?
- helps correct folding
- increases protein stability (particularly significant in secreted proteins)
- cell to cell/ cell to environment adhesion
- immune response
- hormone activity
- embryonic development
What is the purpose of dolichol?
Used to anchor carbohydrates and is where they are built on
Explain the 5 types of glycosylation
- N-linked: glycan binds to aa of Asp in ER (e.g. insulin receptor)
- O-linked: monosaccs bind to OH group serine or threonine in ER, golgi, cytosol & nucleus (e.g. collagen)
- Glypiatan: glycan core links phospholipid & protein (e.g. anchors cell surface proteins)
- C-linked: mannose binds to the indole ring of trytophan (e.g. only in mammalian cells, ECM)
- Phosphoglycosylation: glycan binds to serine via phosphodiester bond
What is acetylation?
The addition/ removal of an acetyl group donated by acetyl co-enzyme A
- can be enzymatic or non using acetylase & deacetylase
When can acetylation occur?
Co or post translational modification
Name the 3 main types of acetylation
- N terminal acetlation
- Lysine acetylation
- Anatagonistic acetylation/ deacetylation
Which type of acetylation is the most common in eukaryotes?
N terminal being used in synthesis, localiation and stability
How is N-terminal acetylation catalysed?
Using N-terminal acetyltransferases (NATs) which transfer an acetyl group to the alpha-amino group of 1st AA residue of protein
- different NATs are responsible for acetylation of nascent protein N termini
Briefly explain lysine acetylation
The transfer of an acetyl group to the primary amine in the ε-position of the lysine side chain within a protein
- involved in activation of gene expression
- often linked to tcn factors (e.g. p53)
Explain the process of antagonistic acetylation/ deacetylation
This method regulates gene expression, occuring in cytoplasm or nucleus (e.g. histones)
- acetylation removes +ve charge from histones so DNA wraps less tightly
- involved in synthesis, stability and localisation of other proteins
How does acetylation affect histones?
Acetylation of histones encourages binding of effector proteins, relaxation of chromatin conformation and increase in txn
High levels of acetylation are associated with what?
Transcriptional hyperactivity
