Cell Communication III

7/24/2019 Cell Communication III

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Which of the following is not one of the majortypes of cell

signaling receptors?

A. Ion-channel-coupled receptors

B. Nuclear receptors

C. Extracellular matrix-coupled receptors

D. Enzyme-coupled receptors

E. G-protein-coupled receptors


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1-

2-

3-


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Hundreds of GPCRs are

concerned with the sense ofsmell


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Halfof all known drugs work through GPCRs


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Signals for GPCRs are highly diverse

Proteins such as chemokines

Peptides such as growth factors

Amino acid deriviatives

Fatty acid derivatives

Hormones such as adrenaline

Neurotransmitters such as acetylcholinePhotons!


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http://www.classwire.com/resources/33/95/3.mov

G protein coupled receptor animation


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Chapter 15

All GPCRs have a similar structure: a single polypeptidechain spanning the cell membrane seven times.

Receptor binding site faces extracellular space; G protein

interaction site is on cytoplasmic side

G-protein coupled receptors (GPCRs)

Inactive

GPCR

Receptor

binding site

G protein

interaction site


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Chapter 15

Garland Science 2008

Trimeric GTP binding protein (G protein)

Inactive G protein

1. It is a trimeric protein made of , , and subunits

2. In the inactive form subunit is bound to GDP, in the active form this is

replaced by GTP

3. The beta subunit is bound to , and

subunits when it is in the inactive state

4. The , and subunits are attached to the plasma membrane through anchors

(covalently attached lipid molecules)

GTPase

domain


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Chapter 15


Activation

GDP released

GTP binds

Dissociation into two activecomponents

Activation of G-protein

Deactivation

GTP hydrolysis

Alpha subunit acts as an

GTPase after binding totarget protein or aregulator

of G protein signaling

(RGS)


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GPCRs activate G proteins by reducing the strength of the GDP binding,

allowing GDP to dissociate and GTP to bind. You have a mutant G protein

which has reduced affinity for GDP and no significant change in the affinity for

GTP.

Which of the following statements is true for the mutant G protein?

A. The mutant G protein will bind GTP irreversibly.

B. Each time the G protein subunit hydrolyzes GTP to GDP, the GDP will

spontaneously dissociate, allowing GTP to bind and reactivate the subunit.

C. The mutant G protein will be constantly inactive.

D. The activity of the mutant G protein will remain the same as the wild type as

the GTP binding is not affected.

E. The mutant G protein will remain in the inactive state until GDP release is

stimulated by interaction with an appropriate GPCR.


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There are twoprincipal signal transduction pathways involving

the G-protein coupled receptors:1)the cAMP signal pathway and

2)the phosphatidylinositol signal pathway


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Chapter 15

G proteins that regulate cyclic AMP production can be

detected by loading cells with fluorescent dyes that

fluoresce at different wavelengths depending on cAMPconcentrations.


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Chapter 15


When activated by Gs

protein adenylyl cyclase

synthesizes cAMP,turning on signal

Cyclic AMP

phosphodiesterases

continuously destroy

cAMP, turning off signal


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An example of intracellular signaling through GPCRs in the stress

response
http://www.youtube.com/watch?v=NMeBZlbs2dU&feature=PlayList&p=603D9A8EA476C1BE&index=0&playnext=1

Cell Communication III

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