CellCommunicationIII

Biology4004
DavidMatthes

Whichofthefollowingisnotoneofthemajortypesofcell
signalingreceptors?
A.Ionchannelcoupledreceptors
B.Nuclearreceptors
C.Extracellularmatrixcoupledreceptors
D.Enzymecoupledreceptors
E.Gproteincoupledreceptors

HundredsofGPCRsare
concernedwiththesenseof
smell

HalfofallknowndrugsworkthroughGPCRs

SignalsforGPCRsarehighlydiverse
Proteinssuchaschemokines
Peptidessuchasgrowthfactors
Aminoacidderiviatives
Fattyacidderivatives
Hormonessuchasadrenaline
Neurotransmitterssuchasacetylcholine
Photons!

Gproteincoupledreceptoranimation

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

Chapter 15

Gproteincoupledreceptors(GPCRs)

Receptor
bindingsite

Inactive
GPCR
Gprotein
interactionsite

AllGPCRshaveasimilarstructure:asinglepolypeptide
chainspanningthecellmembraneseventimes.
Receptorbindingsitefacesextracellularspace;Gprotein
interactionsiteisoncytoplasmicside

Chapter TrimericGTPbindingprotein(Gprotein)
15

GTPase
domain
InactiveGprotein

1. Itisatrimericproteinmadeof,,andsubunits
2. IntheinactiveformsubunitisboundtoGDP,intheactiveformthisis
replacedbyGTP
3. Thebetasubunitisboundto,andsubunitswhenitisintheinactivestate
4. The,andsubunitsareattachedtotheplasmamembranethroughanchors
(covalentlyattachedlipidmolecules)
GarlandScience2008

Chapter 15

ActivationofGprotein

Activation

Deactivation

GDPreleased

GTPhydrolysis

GTPbinds

Alphasubunitactsasan
GTPaseafterbindingto
targetproteinoraregulator
ofGproteinsignaling
(RGS)

Dissociationintotwoactive
components

GarlandScience2008

GPCRsactivateGproteinsbyreducingthestrengthoftheGDPbinding,
allowingGDPtodissociateandGTPtobind.YouhaveamutantGprotein
whichhasreducedaffinityforGDPandnosignificantchangeintheaffinityfor
GTP.
WhichofthefollowingstatementsistrueforthemutantGprotein?
A.ThemutantGproteinwillbindGTPirreversibly.
B.EachtimetheGproteinsubunithydrolyzesGTPtoGDP,theGDPwill
spontaneouslydissociate,allowingGTPtobindandreactivatethesubunit.
C.ThemutantGproteinwillbeconstantlyinactive.
D.TheactivityofthemutantGproteinwillremainthesameasthewildtypeas
theGTPbindingisnotaffected.
E.ThemutantGproteinwillremainintheinactivestateuntilGDPreleaseis
stimulatedbyinteractionwithanappropriateGPCR.

Therearetwoprincipalsignaltransductionpathwaysinvolving
theGproteincoupledreceptors:
1)thecAMPsignalpathwayand
2)thephosphatidylinositolsignalpathway

Chapter 15

GproteinsthatregulatecyclicAMPproductioncanbe
detectedbyloadingcellswithfluorescentdyesthat
fluoresceatdifferentwavelengthsdependingoncAMP
concentrations.

Chapter 15

WhenactivatedbyGs
proteinadenylylcyclase
synthesizescAMP,
turningonsignal
CyclicAMP
phosphodiesterases
continuouslydestroy
cAMP,turningoffsignal
GarlandScience2008

AnexampleofintracellularsignalingthroughGPCRsinthestress
response

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