9 - GPCR 1

Question 1

What defines a GPCR

Answer 1

7 sequence stretches of 25-35 consecutive residues that show a relatively high degree of calculated hydrophobicity

Question 2

What do each sequence represent

Answer 2

7a helices that span the plasma membrane in a counter-clockwise manner forming a receptor

Question 3

How many GPCR proteins . are there

Answer 3

> 800

Question 4

What are some functions of GPCRs

Answer 4

1) Sense extracellular signals
2) Transduce signal intracellularly
3) Act as major drug targets

Question 5

What are some technological advances that propelled GPCR research

Answer 5

1) Radioligand binding techniques
2) Secondary messenger neurochemistry
3) GPCR protein purification
4) GPCR molecular cloning
5) GPCR crystal structure elucidation
6) Cryo-E structure elucidation

Question 6

Where is the ligand activation site in most rhodopsin class

Answer 6

Deep in the extracellular mouth

Question 7

What are the 5 classes of GPCR

Answer 7

G lutamate
R hodopsin
A dhesion
F rizzled/Taste
S ecretin

Question 8

What is the structural determinant of glutamate GPCR

Answer 8

Venus-flytrap domain

Question 9

What is the structural determinant of adhesion GPCR

Answer 9

Adhesion

GAIN

Question 10

What is the structural determinant of frizzle/taste GPCR

Answer 10

Cysteine-rich domain

Question 11

What is the determinant of secretin GPCR

Answer 11

Hormone receptor motif domain

Question 12

What are the exceptions to the ligand activation site being in the extracellular mouth of most rhodopsin

Answer 12

Large peptide receptors

Protease activated receptors

Question 13

What occurs to the ligand in protease activated receptors

Answer 13

Ligand is embedded in the N-terminal but only activated by a protease

Question 14

What does the n-terminus form in the mGluR

Answer 14

Two distinct lobes separated by a cavity

Question 15

What occurs when glutamate binds

Answer 15

Binds in cavity

Causes lobes to close around the ligand (Venus-flytrap)

Question 16

What has a similar mechanism to the mGluR family

Answer 16

GABAb

Question 17

What do adhesion GPCR family have

Answer 17

Large N-terminal

Question 18

What do some adhesion GPCR bind to

Answer 18

ECM proteins

Question 19

How do GPCRs activate G-proteins

Answer 19

Conformational switch from inactive to active state

Question 20

What do GPCRs do

Answer 20

Amplify receptor signal while agonist is resident on receptor

Question 21

What determines the type of signal from GPCRs

Answer 21

a family

Question 22

What does Gs stimulate

Answer 22

cAMP formation

Question 23

What does Gi/o inhibit

Answer 23

cAMP, large BY signal

Question 24

What does Gq stimulate

Answer 24

Phospholipase-C

Mobilise calcium protein kinase-C

Question 25

What are some BY subunit signals (5)

Answer 25

1) Modulate adenylyl cyclase 2) Inhibit N-type calcium channels 3) Activate phospholipase C 4) Activate GIRK potassium channels 5) Activate PI3 kinase

Question 26

What does opening GIRK do

Answer 26

Block action potentials and hyperpolarise the cell membrane

Question 27

What do Gi interact closely with

Answer 27

GIRK channels

Question 28

How does coupling with GIRK and VGCC make Gi inhibitory protiens

Answer 28

GIRK - inhibits action potentials | VGCC - inhibits neurotransmitter release