Jan 21 Flashcards
What are 3 extracellular messenger types?
Small molcules like AA’s, epinephrine, hormones
Gases
Steroids, derived from cholesterol
What are the basics of ligand-gated and steroid hormone receptors?
Ligand-gated= Binding of ligand allows ion flow
Steroid hormone receptors: Hormones pass through MB, then bind to inactive TF in cytosol, then the activated TF goes to nucleus and binds to DNA
How many trans MB helices do GPCRs have? Are GPCRs similar or diff from one other, what tell you about them?
- All GPCRs look quite similar with binding pockets in similar locations. The diff is that the AA’s around the binding pocket are diff. Means that this is ancient protein from early eukaryotes.
What is the largest protein superfamily?
GPCRs
Which eukaryotes have GPCRs?
All of them
What are the roles of the subunits for trimeric G-proteins?
a and y subunit have covalently bound lipids so they insert into inner leaflet of MB. The a subunit is bound to GDP/GTP. When GTP bound it interacts with effector that will generate 2nd messangers.
What is the 1 sentence answer for how rhodopsin works?
Retinol absorbs photon, then rhodopsin changes conformation, helix 6 shifts and exposes docking site for a subunit to bind.
What does adenylate cyclase do when activated?
It is in MB, it turns ATP into cAMP.
When a ligand binds to GPCR, could it activate many heterotrimeric G-proteins with during that same activation from that ligand?
Yes, this means many effectors are activated and get lots of 2nd messenger
What are the steps for 2nd messenger generation following ligand binding to GPCR?
- Ligand binding to GPCR changes cytoplasmic conformation, which increases its affinity for a-subunit of G-protein.
- a-subunit interacting with receptor changes its conformation, so GDP kicked out, and [GTP] is so high it binds next.
- GTP bound a-subunit is active, so it leaves B and y subunits, makes effector make 2nd messenger.
- When GTP hydrolyzed, a joins B and y again
What 3 main things does the Beta gamma complex interact with while alpha has left it?
It interacts with PLC, K+ ion channels, and PI 3-kinase. PI3 kinase and PLC are recruited to MB, ion channels always there
How is G-protein response terminated?
- GPCR in cytoplasmic side is PO4’d by GPCR kinase
- The arrestins bind to GPCR and prevents it activating more G proteins (binding to other a subunits)
What does cholera toxin do/
It inhibits alpha subunits of G-proteins from hydrolyzing GTP, so the G-proteins are always active so get LOTS of cAMP production. Result is epithelial cells to secrete lots of fluid into intestine, so body is severely dehydrated
What does pertussis toxin produced by bordetella do?
It prevents a-subunits from interacting with effectors, so less 2nd messangers, body struggles to fight against bacterial infection.
How were secondary messengers discovered, what was the first?
cAMP. Had cell extract, the hormone activated glycogen phosphorylase. But if spun down extract, it would not work. If resuspended the pellet though, added hormone, then spun down again, then it worked. So we know that need something in MB to produce a soluble something that will then activate the phosphorylase.
