Glycosylation and lipidation Flashcards
Glycans
- covalent, extra-proteinous modifications
- structural/modulatory roles
- diversity of monosaccharides
- produced by Gas
GTs
either use
- dolichol-phosphate precursors or
- oligosaccharide transferases
monosaccharide activation
- nucleotide sugars are linked to anomeric carbon via O-glycosidic bond
- releases monophosphate sugar and phosphate group
Monosaccharide GT donors
- nucleotide diphosphates
Glycan transport
- monophosphate retrograde antiporters
- lumen flippases
N-glycosylation
- on Asn nitrogen side-chain
- targets secreted TM/EC domains
- transferred in sequons
cis-Golgi
- 2x mannose trim
- 1x GlcNac add
- high mannose N glycans
median Golgi
- 3x mannose trim
- 1x GlcNac addition
- 1x fucose addition
- 1x GlcNac addition
trans Golgi
- 3x galactose addition
- 3x silica acid addition
- complex, heterogenous glycans
N-glycosylation polymorphism in spike
- spike = 22 sequons
- stabilises RBD dynamics and recognition
O-glycosylation
- on Ser/Thr et al.
- targets EC/cytoplasmic domains
- classified on 1st monosaccharide
pro-hydroxylation
- prolyl hydroxylases
- collagen
lys-hydroxylation
- Lysyl hydroxylases
- collagen
tyr-hydroxylation
- glycogenin
- glycogen primer
GalNac
- initiated in Golgi
GalNac transferases
- approx 20 types
- generate 8 core glycans
- e.g. IgM1, IgG3 hinge regions, protease protection
galactose O-glycosylation
- O-glycan polymorphism on glycophorin caused by different GT expression
- IgM recognises during blood transfusion
mannose
- initiated in ER, completed in Golgi
- alpha-dystroglycan in muscle links exoskeleton to cytoskeleton
arabinose
- on hydroxyproline in SPPP repeat
- extensins for cell wall expansion
GPI
- catalysed by GPI transamidase
GPI regulation
- lipid tail modification
- phospholipase C hydrolyses lipid double tail
Example of GPI
- Matrix Metallo Proteases
- high in metastatic cancers
Palmitoylation
- S-acylation on Cys residues
- O-acylation on Ser/Thr
- non consensus motif
- > 2000 proteins per cell
- catalysed by PATs
- palmitoyl-CoA substrate
PATs
- 23 in mammals
- 23 in plants
- TM, catalytic DHHC motif
- enriched in Golgi
Depalmitoylation
- acyl-protein thioesterases
- multiple lipid tails per protein
Palmitoylation function
cargo concentration at cisternal rim
Myristoylation
- onto N-terminal glycine
- NMTs
- eukaryotic
co-translational myristoylation
methionine aminopeptidase exposes N-terminal glycine
post-translational myristoylation
caspase end-protease cleaves protein
myristoylation example
- BID myristoylation
Prenylation
- on Cys motif
- C-terminal residue removal
- -COOH methylated by cytoplasmic ER integral proteins