Receptors

Question 1

basic signal transduction pathway

Answer 1

Signal outside cell is recognized, signal transmitted across membrane, cell elicits response (usually cascades of enzymes)

Question 2

5 features of signal transduction systems

Answer 2

Specificity, Amplification, Modularity, Desensitization/Adaptation, Integration

Question 3

Specificity

Answer 3

signal molec is specific to receptor

Question 4

Amplification

Answer 4

enzyme affects enzymes -> number of affected molecules increases geometrically in cascade

Question 5

Modularity

Answer 5

proteins can have multiple signals converge on them (dampen/strengthen signal), forms diverse signaling complexes

Question 6

Desensitization/Adaptation

Answer 6

feedback inhibition, shuts off receptor or removes it from cell surface

Question 7

Integration

Answer 7

mult signals affect mult receptors, the regularity outcome results from the integrated input from both receptors (either additive or inhibitive)

Question 8

3 families of membrane bound signal transduction receptor molecules

Answer 8

ion channel linked receptors, G protein linked receptors, enzyme linked receptors

Question 9

3 domains of G protein linked receptors and enzyme linked receptors

Answer 9

extracellular domain, transmembrane domain, intracelluar domain

(Tooze 251)

Question 10

purpose of a membrane receptor’s extracellular domain

Answer 10

signal recognition

Question 11

purpose of a membrane receptor’s transmembrane domain

Answer 11

signal transmission

Question 12

purpose of a membrane receptor’s intracelluar domain

Answer 12

signal response and amplification

Question 13

G proteins

Answer 13

bind guanaine nucleotides, act as molecular switches, activated by binding to GTP, inactivated when GTP hydrolyzed to GDP

Question 14

How is the hydrolysis of GTP catalyzed?

Answer 14

done by the G protein itself (but does not turn itself off w/out help since it is a slow GTPase)

Question 15

How is G protein turned off?

Answer 15

G protein itself is a slow GTPase, accelerated w/RGS
(regulators of GTP hydrolysis), binds to active G protein, incr rate of GTP hydrolysis

once hydrolyzed, α unit rebinds to beta-gamma unit

Question 16

G protein structure

Answer 16

most are heterotrimers (α, ß, γ subunits) attached to the cytosolic domain, alpha and gamma bound to membrane by lipids, beta not bound but is always complexed with gamma

Question 17

Which G protein subunit contains GTPase activity?

Answer 17

alpha subunit

Question 18

How does G protein break into subunits?

Answer 18

heterotrimer will dissociate into the alpha subunit and the beta-gamma heterodimer, each indep transmit the signal they received from the same receptor, move onto dif effectors

Question 19

characteristics of membrane receptors that control the senses/other main physiological responses (GPCR’s)

Answer 19

contain 7 transmembrane helices, signals amplified by G proteins

Question 20

How is G protein turned on?

Answer 20

ligand binds to extracelluar domain, receptor undergoes confirmational change, activates cytosolic domain, catalyzes GDP switching for GTP, G protein activated, released, dissociates

Question 22

How are secondary messengers produced?

Answer 22

active Gα-GTP complexed with effector molec, triggers production of secondary messengers

Question 23

Ras proteins

Answer 23

GTP binding protein, regulators of signal transduction processes leading to cell multiplication and differentiation, molecular switches activated w/protein tyrosine kinase receptors, activity depends on GTP/GDP

Question 23

How to turn off Ras proteins?

Answer 23

switched off w/GAP (GTPase activating protein), turns off very slowly w/out GAP

Question 24

RAS structure

Answer 24

6 B sheets (5 are parallel), 5 A helices surround sheet

Question 25

receptor tyrosine kinases

Answer 25

catalyzes the transfer of phosphate groups to tyrosine, comes together to form a dimer, activates the Tyr groups (ready to transfer P groups )

Question 26

How do receptor tyrosine kinases cause celluar response?

Answer 26

relay proteins bind to P groups on Tyr, one responses for each relay protein that binds to P group

Question 27

Cholera toxin

Answer 27

failure to turn off GTP-activated Gα, binds to Gα, prevents GTP hydrolysis, can't stop signaling, results in continued sodium/water excretion to gut

Question 28

What leads to uncontrollable cell growth?

Answer 28

RAS mutated, can't be activated to turn off GTP-activated Gα, prevents GTP hydrolysis, can't stop signaling

Question 29

RAS binding pocket structure

Answer 29

loop regions binding the B strands and A helices

Question 30

Where is GTP bound in RAS?

Answer 30

pocket at the C-term of B strands

Question 31

RAS and Gα use MG2+ ions for what?

Answer 31

stabilize guanine nucleotide complex, weaken P-O that gets split for catalysis

Question 32

Why does RAS take so long to hydrolyze GTP w/out GAP?

Answer 32

lacks the Arg that stabilizes the negative charge on the phosphate, GAP supplies the necessary Arg

Question 33

transducin

Answer 33

G protein that mediates light adaptation in retinal rods

Question 34

phosducin purpose

Answer 34

G protein regulator molecule, reduces transducin sensitivity, blocks Gα binding site, binds Gß and pulls it into the cytoplasm where it is inactive

Question 35

Rhodopsin mech

Answer 35

Receptor (rhodopsin) absorbs photons, activates G-protein (transducin), which activates cGMP phosophodiesterase, degrades cGMP to GMP

Question 36

Gß structure

Answer 36

7 stranded B propeller, each blade is 4 antiparallel B sheet

Question 37

Gγ structure

Answer 37

A helix, stabilized by Gß | Tooze 263

Question 38

Gα structure

Answer 38

3 switch regions

Question 39

6 general types of signal transducers

Answer 39

G protein coupled receptors, receptor tyrosine kinases, receptor guanylyl cyclases, gated ion channels, adhesion receptors, nuclear recptors

Question 40

eg of G protein coupled receptors

Answer 40

Ras, ß-adrenergic receptor

Question 41

eg of receptor tyrosine kinases

Answer 41

insulin receptor, growth hormone, epidermal growth factor receptor

Question 42

eg of gated ion channels

Answer 42

voltage gated K+ channels, nAChR

Question 43

how are G proteins efficient?

Answer 43

can be amplified at 2 steps: active receptor can activate mult G proteins each downstream target can produce many secondary messengers

Question 44

ß-adrenergic receptor

Answer 44

ligand: epinephrine receptor: ß-adrenergic receptor effector: adenylate cyclase secondary messenger: cycle AMP response: glycogen breakdown (cAMP activates protein kinase A)

Question 45

Human Growth Hormone structure

Answer 45

4 helix bundle; up, up, down, down

Question 46

domains of hormone receptors

Answer 46

3 domains: EC ligand binding domain, single transmembrane domain, IC domain

Question 47

Human Growth Hormone Receptor structure

Answer 47

consists of just the EC domain, 2 immunoglobulin-like chains, two forms dimer, 4 sets of 7 (Tooze 267)

Question 48

How does the Human Growth Hormone dimerize?

Answer 48

occurs sequentially, cross phosphorylation: GH binds to 1st subunit which brings the 2nd subunit together, aided by noncatalytic proteins that hold together other protein molec

Question 49

Cross talk

Answer 49

ß adrenergic receptor “talks” to the insulin receptor