GPCRs

Question 1

describe the general scheme of GPCR signaling

Answer 1

1. ligand binds to extracellular domain of receptor, inducing a conformational change in receptor
2. when inactive Gprotein associates with ligand-bound receptor, the receptor helps the alpha subunit turn GDP into GTP, activating the G protein
3. alpha subunit separates from beta-gamma dimer.
   - alpha is active unitl its innate GTPase activity hydrolyzes GTP
   - beta-gamma dimer is active as long as it is separated from alpha
4. actvated G protein components affect downstream targets
   - ex: some activated alpha subunits can activate adenylyl cyclase to convert ATP to cAMP

Question 2

What are the functions of GEF’s (guanine nucleotide exchange factors), GAP’s (GTPase Activator Proteins), and RGS’s (Regulators of G Protein Signaling)?

Answer 2

• regulate GTPase activity of alpha subunit of G protein
• control how long the G proteins are activated for

Question 3

are all G-protein subunits the same?

Answer 3

• no, there are multiple family members of each G protein subunit
• some will activate signaling pathways, others will inhibit signaling pathways

Question 3

what are 3 examples of second messengers?

Answer 3

1. cAMP
2. calcium ions
3. PIP2

Question 4

what type of molecules is PIP2 and what signaling molecules can be made from it? what type of enzyme is involved in that process?

Answer 4

• it is a type of membrane phospholipid
• IP3 is the signaling molecule that can be made from it
• DAG (diacylglyceride) is also madae
• Phospholipase C (PLC) cleave PIP2 into IP3 (enzyme activated by G-protein)