Lecture 4

Question 1

GPCR functional diversity

Answer 1

conical in structure but diverse in function

Question 2

how many domains does GPCR have

Answer 2

8 hydrophilic (water-loving) domains interrupted by 7 lipophilic (lipid-loving) domains

Question 3

how many extra-and intracellular loops

Answer 3

3 each
E2,3,4
C1,2,3

Question 4

____________ to

allow the ligand to bind in the pocket

Answer 4

TM domains make a water-soluble pocket

Question 5

__________ and membrane proximal part of
C-terminal domain – important for G protein
coupling to transmembrane signaling

Answer 5

C3, part of C2

Question 6

___________ are important for receptor

de-sensitization and regulation

Answer 6

C3 and C-terminal tail

Question 7

where do GPCR have diversity

Answer 7

Diversity in N-terminal domain, C3 loop

and C-terminal domain

Question 8

_____________ was first hormone GPCR purified and cloned

Answer 8

β2-adrenergic receptor (β2AR)

Question 9

_________ was the first GPCR

Answer 9

rhodopsin

Question 10

what is the receptor to Positively charged NH3

Answer 10

Negative charge (D) Asp-COO-(D) on TM3 I

Question 11

what is a receptor to Flat aromatic catechol ring on ligand
sits under F and above Tryptophan
(W) – two flat amino acids

Answer 11

F) Aromatic Phe (F) ring on TM4

Question 12

what is the recpetor to Catechol-OHs (hydroxyl)

Answer 12

Two (S) Ser-OHs (S) on TM5

Question 13

what are the Four critical contact points for Norepinephrine binding

Answer 13

D, S,S,F

Question 14

Small molecule ligands bind about _______of the way into

the membrane

Answer 14

1/3

Question 15

_____________ is Synthesized from ATP by membrane-bound enzyme adenylyl cyclase (AC)

Answer 15

cAMP

Question 16

_____________ deactivates adenylyl cyclase

Answer 16

GDP

Question 17

____________ stimulates AC enzyme directly independent of

hormone, receptor, and GTP or G protein

Answer 17

Forskolin

Question 18

Receptor (hormone binding)_____________
G protein Gs (GTP binding and hydrolysis) _______________
Adenylyl Cyclase (cAMP “second messenger” formation) ______________

Answer 18

Receptor (hormone binding)  provides specificity

G protein Gs (GTP binding and hydrolysis)  provides signal transduction

Adenylyl Cyclase (cAMP “second messenger” formation)  causes effects

Question 19

what are the large families of G proteins

how are they similar

Answer 19

Gs, Gi, Gq/11 G12/13

▪ All four have similar structures and identical mechanisms of activation

Question 20

what G protein do these use
Beta adrenergic
Alpha 2
Alpha 1

Answer 20

Gs
Gi
Gq

Question 21

G proteins are membrane attached by ______________on α and γ subunits

Answer 21

attached by lipid anchors (fatty acid chains)

Question 22

______________ are nonhydrolyzable GTP analogs

Answer 22

GTPrS

GppNHp

Question 23

which subunit has intrinsic GTPase

what does GTPase do?

Answer 23

alpha subunit

turn off

Question 24

what is the slowest step in GPCR activation

Answer 24

GDP release

Question 25

explain bidirectional regulation of AC

Answer 25

▪ Gs effectors and mechanisms
▪ Gs stimulates adenylyl cyclase
▪ but can also activate or inhibit ion channels
▪ in some cases by α subunits, other cases by βγ subunits
▪ Gi effectors and mechanisms
▪ Gi inhibits adenylyl cyclase
▪ but can also activate or inhibit ion channels
▪ in some cases by α subunits, other cases by βγ subunits

Question 26

ADP ribosylation happens to what

Answer 26

G-proteins

Question 27

Cholera Toxin

Answer 27

Irreversibly INactivates GTPase activity of Gs

ADP-ribose is attached in GTPase catalytic site of Gsα subunit

Cholera toxin mimics GS-coupled receptor action

Question 28

Pertussis Toxin

Answer 28

irreversibly activates AC and cAMP production
Irreversibly blocks Gi activation by preventing R-Gi “coupling”

Pertussis toxin prevents Gi
-coupled receptor action