Small PTMs Flashcards
ATP
- always in excess
- recycled 1000-1500 times/day
phosphorylation targets
- polar (OH side chains)
- basic
- acidic
- Cys
A. kinome
918
Protein Kinase A
- aka cAMP-dependent protein kinase
- promotes glycogen -> glucose during flight/fight (but multifunctional)
- 290aa kinase domain
- regulated by Regulatory Subunit
Protein kinase A cascade
1) phosphorylates phosphorylase kinase
2) phosphorylates glycogen phosphorylase
3) glycogen -> glucose-1-phosphate
PKA activation
1) adrenaline activates GPCR
2) GPalpha released, binds to adenylate cyclase
3) Regulatory subunit dissociates from cAMP
4) phosphorylated by PDK1 in activation loop; folds to orient catalytic residues
PKA inactivation
- cAMP hydrolysis
- Regulatory subunit binds
Dephosphorylation
- 189 in humans (mostly for cysteine)
- 0.89% proteome
- 10 different folds
Methylation
- can occur on acidic and basic N and C termini
- N and O methylation
- S-adenosyl-methionine derived using MT
MTs
- humans: 51
- A. thaliana: 49
- SET domains
His methylation
- SETD8 methylates beta-actin His73
- decreases ATP-hydrolysis
- setd3 knockout: reduced progeny due to birth defects
Lys methylation
- FliB methylates Salmonella
- promotes hydrophobic cell adhesion and invasion via hydrophobic epithelial interaction
H3K4me
active
H3K9me
constitutive heterochromatin
H3K27me
facultative heterochromatin
Demethylation
- O-methylation requires hydrolysis, releasing methanol
- N-methylation requires FAD-cofactor reduction and hydrolysis
- lysine specific HDMs
acetylation
- general at N-terminus
- regulatory at Lys
N-terminal acetylation
- 85% human proteins
- NATs with GNAT domains
NATs
- 8 in eukaryotes
- 3 in bacteria
- 1 in archaea
Lysine acetylation
KATs, HATs and GNATs
KATs
- 17 in humans
- 12 in arabidopsis
Deacetylation
- KDACs, HDACs (share the same KDAC fold)
- 18 in humans and arabidopsis
H3K27ac
activates transcription