HUANG - LECTURE 2 Flashcards
what is phosphorylation
what is lipidation
anchors to the membrane
reversible process: turn on and off by regulating the localization
what is disulfide bond modification
covalently links the “S” atoms of two different cysteine residues
usually happens outside the cell, needs to be in a more oxidized environment
not a very common modification
what is acetylation
what can protein modifications do
example of phosphorylation influencing localization
example of phosphorylation influencing protein-protein interactions
what can be glycosylated?
proteins and lipids
different between a glycoprotein and a proteoglycan
what are the functions of glycosylation
phosphorylation is prevented by O-linked glycosylation
how is c-Myc regulated by both phosphorylation and glycosylation?
- c-Myc can be phosphorylated by ERK, which leds to its stabilization (on Ser62)
- it can also be phosphorylated (Thr58) again by GSK3beta, which promotes the removal of the Ser62 phosphate, and leads to the ubiquitination and degradation of c-Myc
- c-Myc can also be glycosylated by OGT on Thr58, which leads to its stabilization
what are the modifications that can be done to sugars
what are the primary sugars
what are the different sugars and where are they made
what are the most common sites of glycosylation
what are the functions of O-linked glycosylation and where do those functions manifest?
protection and water retention are the major functions
shown in the ECM, synovial fluid in joints, mucus and others
also blocks phosphorylation
when can glycosylation occur?
post or co translationally
which enzymes are responsible for glycosylation and what motif do they recognise?
what is the first step of biosynthesis of all N-linked oligosaccharides
what is the structure of the precursor Glc3Man9(GlcNac)2
what are the types of N-linked glycoproteins
high mannose, hybrid and complex
what is the structure of dolichol
what are the steps of Dolichol-PP-oligosaccharide synthesis
what can now N-linked glycoproteins do?
what happens for N-linked glycoproteins to mature in the ER?
what happens to glycoproteins once they reach the golgi after being done in the ER?
nucleotide sugars don’t have to be imported into the ER, as they are donated to dolichol and then flipped
what are the relative amounts of High mannose, hybrid and complex sugars throughout the ER and the GA?
how do the nucleotide sugars get into the golgi?
example of the role of glycosylation in cancer
cancers upregulate PDL-1 (which is glycosylated) and bind to the PD-1 receptors on effector T cells
this has an effect of immunosuppression and T cells cannot kill those cancer cells anymore
a therapy sequesters those PDL1 receptors, and can also be endocytosed inside the cancer cell to induce cell death
how can cancer altered glycosylation enter the bloodstream
how are glycoproteins targeted to the lysosome?
how are proteins brought from the GA to the lysosome?
what does UGGT do?
reverse effect of glucosidase II
adds sugar residues back
involved in ER quality control processing
how does the protein folding quality control work
what happens if proteins still cannot properly fold despite multiple rounds with UGGT?
goes into ERAD (ER associated degradation)
EDEM recognises misfolded proteins and recruits additional chaperones
BiP escorts to the membrane, where it will be exported and degraded in the proteasome
what is the UPR
if a lot of ERAD is happening, general protein synthesis is paused
selective transcription/translation of chaperones, foldases, ERAD components and apoptosis
