III. Signal transduction and cell cycle | 39. Types and functions of GTP-binding proteins in signaling

Question 1

I. G proteins
1. What are G-proteins?

Answer 1

GTP-binding proteins are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a stimulus outside a cell to its interior

Question 2

I. G proteins
2. What are the 2 main classes of G-proteins?

Answer 2

There are two main classes of GTP-binding proteins:
1. monomeric (small) G-proteins
2. heterotrimeric (large) G-proteins.

Question 3

I. G proteins
3. The general concept of G-protein activation/inactivation is true for both monomeric and heterotrimeric G-proteins
=> T/F?

Answer 3

True!!!

Question 4

I. G proteins
4. Explain The general concept of G-protein activation/inactivation

Answer 4

The general concept of G-protein activation/inactivation is true for both monomeric and heterotrimeric G-proteins:
- In the active state, they are bound to GTP. They can influence their target cells
=> ACTIVATION: exchange of GDP for GTP
- In the inactive state, they are bound to GDP. They cannot influence their target cells
=> INACTIVATION: GTP hydrolyzed to GDP + Pi

Question 5

II. Heterotrimeric G-proteins
1. What are the features of heterotrimeric G-proteins?

Answer 5

Heterotrimeric G-proteins are anchored to the plasma membrane in the cell and are activated by 7TM G-protein-coupled receptors (GPCRs)

Question 6

II. Heterotrimeric G-proteins
2. What is the structure of heterotrimeric G-proteins?

Answer 6

• The heterotrimeric G-proteins are composed of 3 subunits: α, β, γ

Question 7

II. Heterotrimeric G-proteins
3. What is the mechanism of Heterotrimeric G-proteins?

Answer 7

• In the absence of a ligand, G-proteins are inactive -> form a heterotrimeric complex
  with GDP binding to the α-subunit
• Binding of an extracellular ligand to the GPCR -> induce a conformational change in
  G-proteins -> release of GDP -> α-subunit will dissociate from the heterotrimeric
  complex and bind GTP instead -> will have an α-GTP complex and a βγ-dimer
• Both the α-GTP complex and βγ-dimer can activate different signaling cascades and
  effector proteins, until the α-subunit (has intrinsic GTPase activity) hydrolyzes the attached GTP to GDP + Pi -> the subunits will reassociate

Question 8

II. Heterotrimeric G-proteins
4A. List different G-protein α-subunits?

Answer 8

• Gs (stimulating)
• Gi (inhibitory)
• Gq
• Gt (= transducin)

Question 9

II. Heterotrimeric G-proteins - different G-protein α-subunits
4B. What is the role of Gs?

Answer 9

Gs (stimulating) activates adenylate cyclase, which produces cAMP from ATP. cAMP will act as a 2nd messenger and activate PKA which can phosphorylate downstream targets

Question 10

II. Heterotrimeric G-proteins - different G-protein α-subunits
4C. What is the role of Gi?

Answer 10

• Gi (inhibitory) inhibits adenylyl cyclase, leading to decreased levels of cAMP.
• cAMP will be degraded to AMP by AMP phosphodiesterase

Question 11

II. Heterotrimeric G-proteins - different G-protein α-subunits
4D. What is the role of Gq?

Answer 11

• Gq activates phospholipase C enzymes (PLC), which cleave phosphoinositol-4,5- bisphosphate (PIP2) to inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
• The inositol phospholipid dependent pathway is used as a signal transduction pathway for many hormones

Question 12

II. Heterotrimeric G-proteins - different G-protein α-subunits
4E. What is the role of Gt?

Answer 12

• Gt (= transducin) activates phosphodiesterase in photoreceptor cells (rods and cones), resulting in breakdown of cGMP to GMP.
• Is important in photo transduction (light converted to electrical signals)

Question 13

III. Monomeric G-proteins
1. What are monomeric G-proteins?

Answer 13

• Also known as small GTPases and belong to the Ras superfamily GTPases
• Are composed of a single polypeptide chain

Question 14

III. Monomeric G-proteins
2. What is the mechanism of monomeric G-proteins?

Answer 14

• They also bind GTP and GDP, and are involved in signal transduction
• They are activated by the exchange of GDP for GTP, which is mediated by Guanine nucleotide exchange factors (GEFs)
• Since the small GTPases have very low intrinsic GTPase activity, it will be increased by GTPase Activating Proteins (GAPs), that inactivate the small GTPases
  => THE NAME IS COUNTER-INTUITIVE
  => Ras can also be activated by SOS and growth factors