L02 Flashcards
what are the features of post translational modification PMT
covalent addition to or cleavage of proteins
After protein biosynthesis
important component of cell signalling
occurs on the amino-acid chain or at a terminal
extending the 21 aa’s available
PMT can be reversible or irreversible
True
what are the types of PMTs
cleavage
methylation
acetylation
disulfide bond
glycosylation
phosphorylation
when would cleavage take place
secondary structure or beyond
what protein is an example for PMT cleavage
insulin
what peptide is removed from insulin
C
what produces mature insulin
carboxypeptidase E
what are the features of phosphorylation
One of the most common/well studied
1/3 of cellular proteins thought to be phosphorylated at any given time
reversibly add/remove phosphate
causes conformational change in the protein
activate or deactivate an enzyme (phosphate has 2 neg charges so causes conformational change)
activation forms a site recognised by other proteins
deactivation can mask a binding site preventing protein -protein interaction
what are protein kinases
Enzymes that catalyse the transfer of a phosphate group from a high energy donor molecule to a specific substrate- phosphorylation
how many protein kinases are characterised so far
513
how many protein kinases have a homologous catalytic domain
478
phosphorylation is unidirectional
true
what are phosphatases
enzyme catalyse the removal of a phosphate group from a substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group (dephosphorylation
protein phosphatases are often in a chain
True
what is glycosylation
a carbohydrate (monosaccharide to complex) is covalently bound to a functional group (e.g. hydroxyl) on a protein, via a glycosidic bond
how many glycosylation disorders
40
glycosylation is Built on Dolichol- which ‘anchors’ to the membrane
true
what are the types of glycosylation
N-linked
O-linked
Glypiation
C-linked
Phosphogly-cosylation
what are the features of N-linked glycosylation
Glycan bind to the amino group of asparagine
happens in the ER
examples: insulin receptor, ECM, regulation
what are the features of O-linked glycosylation
Monosaccharides bind to the hydroxyl group serine or threonine
happens in ER, Golgi, cystosol and nucleus
example: collagen, a number of pathogenic bacteria (e.g. clostridium toxins)
what are the features of glypiation glycosylation
Glycan core links a phospholipid and a protein
example: anchors cell surface proteins
what are the features of C-linked glycosylation
Mannose binds to the indole ring of tryptophan
Example: only mammalian cells, ECM
what are the features of Phosphogly-cosylation glycosylation
Glycan binds to serine via phosphodiester bond
what are the features of Acetylation
- addition or removal of an acetyl group
- donated by acetyl co-enzyme A
- Can be enzymatic or non-enzymatic
- enyzmes involve Acetylase or Deacetylase
- co- or post-translational modification
-80-90% of human proteins are co-trans acetylated at the Nα-termini of the nascent polypeptide chains
-co- = modification of an amino acid as the translation occurs
- particular proteins are chromosome related and this indicates its importance in gene expression
what are the types of acetylation
N-terminal
Lysine acetylatio
what are the features of N-terminal acetylation
- most common co-transational modification in eukaryotes
- synthesis
localisation
stability - 80-90% of human proteins
what are the features of Lysine acetylation
- often acetylation and deacetylation cycle is linked to transcription factors (e.g. p53)
- activation of gene expression
features of acetylation in histones
Histone acetyltransferase/deacetylase (HDAC or HAT, now KDAC and KAT)
Located in cytoplasm or nucleus
Acetylation removes the +ve charge from the histone
meaning the DNA wraps less tightly
acetylation of histones encourages binding of effector proteins, relaxation of chromatin conformation, and an increase in transcription
also in the synthesis, stability and localization of other proteins.
High level acetylation associated with transcriptional hyperactivity
which amino acids undergo methylation
lysine (once, twice or three times)
arginine (once or twice)
which enzyme reverses methylation
demethylase
what is an example of a molecule that donates a methyl group
S-adenosylmethionine
compare carbonyl methylation to nitrogen methylation
carbonyl methylation is generally reversible and used to modulate a reaction
nitrogen methylation however are generally irreversible creating new amino acids
compare lysine methylation and arginine methylation
arginine methylation
- regulation of RNA processing
- Gene transcription
- DNA damage repair
- protein translocation
- signal transduction
lysine methylation
- histone function regulation
- epigenetic regulation of transcription
- Lysine Methyltrasferase (KMT)
