BIOL 2021 Lecture Notes - Protein Kinase A, Adenylyl Cyclase, Cyclic Adenosine Monophosphate

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16 Oct 2011
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BIOL 2021- April 15 2009
CHAPTER 15 PART 2: CELL COMMUNICATION
G PROTEIN COUPLED RECEPTORS (GPCR)
- Largest family
- On surface
- Take signals from the outside and transfer them
- 700 GPCR in human genome
- ½ of all drugs are targeted to these receptors/pathways
- Always a multipass transmembrane protein with a 7 MEMBRANE SPAN (passes through the
plasma membrane 7 times)
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Figure 1 G proteins
- GPCR work through trimeric G-protein (3 subunits)
Alpha subunit binds GDP
Beta and gamma subunits form a complex
Alpha and gamma subunits are membrane bound and have fatty acids integral in plasma
membrane
There are many G proteins that are specific for GPCR and target
Figure 2 Monomeric G protein (1 subunit)
- In trimeric proteins, GEF activated the exchange of GDP for GTP on GPCR (activating pathway)
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- Active receptor cause a conformational change of G protein to give an active G protein
- Then GDP is exchanged for GTP (activated)
- Many G proteins are activated by active receptors
- Amplification-> small signal amplified to cause a big signal
- Targets can be on ion channels or enzymes
- Signal is ended by alpha GTPase which hydrolyses GTP-> GDP, making it inactive
- TO inactivate receptor, receptor gets phosphorylated (receptor kinase)
Then arrestin protein binds which prevents it from activating any more G proteins
Αβγ inactive (GDP bound)
Separates to: α (active) and βγ (active)
Hydrolysis of GTP: GDP-αβγ (inactive- α reconnect with βγ)
Targets: enzyme produced small intracellular mediators (second messengers)
2 PATHWAYS
- Cyclic AMP (CAMP) produced
- Found in all animal cells, prokaryotes but NOT PLANTS
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