Lecture 12 Flashcards
What is citrullination
An Argenine deamination PTM
Enzyme PAD makes the postive charge guanidinuim become neutral by turning =nh2+ into =O
Still polar
PAD and all of its isoforms are
Calcium dependent
What are NETs
Neutrophil extracellular traps
Form due to histone citrullination
What is lytic net formation
This is dependent on the ROS stress pathway (reactive oxygen species)
The ROS pathway activates pad 4
Pad 4 citrullinates histones
Chromatin decondenses and forms NETs
Neutrophil gets lysed to remove the NET and the trapped material
What things use lytic net formation
Fungus and virus
What is (non lytic) net pathway
Activated by bacteria like e coli
The cell has TLR receptors (toll like receptors) thatt tecongize s.aureus or r coli
This receptor activate PAD 4 and nets are made
But the nets get secreted out of the cell
Histones can also act as
Antimocrobials
They can be secreted at part of the nets because they have anti microbial properties
What prevents citrullination on histones
Prior Methylation of the arg side chains
What happens to histones during various infections
Citrullination of them increases
This leads to the NETosis pathway
What is a disease caused by too much or a specific cltrullinated protein
MS- multiple sclerosis
What there’s too much myelin basic protien
Where does cirulination generally occur when it is a problem
Should only be inside the cell
If happen outside cell this is a sign that something is wrong and the proteins are recognized as non self by the immune system
What is special about rheumatoid arthritis patients and cirullinated proteins
They have antibodies against these proteins in their blood
These antibodies can be used as bio markers to diagnose people
Because the citrullinated protiens are recognized as non self by the immune system
What diseases are caused by citrullination
Sepsis
Kidney disease
Periodontis
What is special about some Covid patients and netosis
The netosis pathway in them leads to blood clotting
They need more respiratory support and have less survival
This is rare
What is special about some Covid patients and netosis
The netosis pathway in them leads to blood clotting
They need more respiratory support and have less survival
This is rate
What are the three ways to target proteins toward cell membranes
what do these all occur on
Myristoylation
Palmitoylation
Prenylation (also called hers geranyl geranylation )
All on cysteines
Where does myrisotylation occur
When is is done and is it reversible
Only at the n terminal glycine , intracellular
Done during protein folding (cotranslational)
Irreversible
What enzyme puts myristoyl groups onto the glycine
N-myristoyltransferase
Makes the protein a peripheral membrane protein
Give an example of something that’s been myristoylated
Recoverin
What is recoverin
A calcium myristoyl switch protein
Meaning when binding calcium, it exposes its hidden mysristotl group
Then gets anchored to the membrane
How does recoverin function in dark
In light
It’s found in photoreceptors in the eye
It regulates the activity of rhodopsin kinase (phosohylrates rhodopsin to inactivate it)
In dark: recoverin binds ca, inhibits rhodopsin kinase. So now rhodopsin works and light response is longer
In light: ca low, recoverin not active. Rhodopsin kinase active, rhodopsin inactive and dark state is prolonged
What is the holo and apo state of recoverin
Holo: ca bound, mystical exposed
Apo: no ca, myristoyl buried
Recovering has how many EF hands
How many of them actually bind to ca
4
2
What type of bond is myristoyl
Thioester
