L6 Post Translational Modifications Flashcards
types of post translational modifications (PMTs)
glycosylation, phosphorylation, acetylation, methylation and ubiquitination
significance of PMTs in cellular functions
regulation of activity: phosphorylation > activation > metabolic regulation
signal transduction
protein stability: ubiquitination and sumolyation mark proteins for degradation or stabilisation
cellular localisation: certain modifications can influence where proteins localised
protein-protein interactions: create new interaction sites or disrupt existing ones
definition of glycosylation
addition of saccharides (sugars) to proteins and lipids (enzyme directed and site specific)
occurs mainly in RER and Golgi
types of glycosylation
N-linked: when sugar attached to N atom in side chain of asparagine
O-linked: when sugar molecules attached to O atom in side chain of serine or threonine
Dolichol-mediated: the use of dolichol, a polyisoprenol lipid as carrier for adding sugars to nascent proteins; dolichol is embedded in lipid bilayer and plays key role in N-linked glycosylation
what is dolichol
a polyisoprenol lipid comprised of five-carbon isoprene units linked linearly in head-to-tail fashion > embedded in lipid bilayer
biological and cellular functions of glycosylation
protein folding and stability
cell-cell recognition and communication
immune response via antigen recognition
blood group determination
definition of phosphorylation
the addition of a phosphate group to protein, typically one serine, tyrosine or threonine residues
reversible and dynamic process
kinases add P groups, phosphates remove them
role of phosphorylation in cellular activity
substrate specificity: different kinases got different substrates
regulation of protein functions: can activate or deactivate enzymes and receptors
signal transduction: transmission of signals from cell surface to interior
definition of acetylation
addition of acetyl groups to proteins at lysine residues
histone acetyltransferases (HATs): add acetyl groups
histone deacetylases (HDACs): removes them
mechanism of acetylation
reduces positive charges on histone > decrease affinity for negatively charged DNA > relax chromatin structure > more access for transcription factors > increase gene expression
usually involved in epigenetic control mechanisms: changes that affect gene expression without altering DNA itself
definition of methylation
addition of methyl group to protein on lysine or arginine residues > important role gene expression and protein function
histone methyltransferases (HMTs): add methyl groups
demethylases: remove methyl groups
impact of histone methylation on gene expression very dependent on which histone and which lysine residue
relation between acetylation and methylation
when methylation happens after deacetylation, usually linked to gene silencing > heterochromatin formation > long term gene repression
what is Protein Arginine Methyltransferases (PRMTs)
enzymes that specifically methylate arginine residues on both histones and non histone proteins
definition of ubiquitination
attachment of small regulatory protein to substrate protein
mechanism of ubiquitination
ubiquitin attached via C-terminal glycine residue to elipson amino group substrate lysine residue
reaction performed by a three step enzymatic cascade
steps of ubiquitination involving E1-E3
E1 activates ubiquitin using ATP > forms thioester bond between E1 and ubiquitin
E1 transfers ubiquitin to E2 catalytic cysteine
E3 binds E2 and substrate > helps transfer ubiquitin from E2 to lysine side chain of substrate > forms isopeptide bond
difference between peptide and isopeptide bond
peptide bond: between alpha-amino group of one a.a and alpha-carboxyl group of another a.a
isopeptide bond: between alpha-amino group of one a.a and non alpha-carboxyl group of another a.a (usually side chains)
