G protein coupled receptors Flashcards
g protein coupled receptors are — protein w MW of 35k-70k
they pass the membrane —– times
at least — different types of receptors
these include:
- monomeric
- 7 times
- 500
- light taste smell receptors and neurotransmitters
key points of g-proteins:
1. an enzyme composed of — units which are:
2. binds to and hydrolysis —- to —
3. —- when GDP bound
4.—- when GTP bound
5. acquires — affinity for GTP when its associated receptor is activated
- 3 subunits alpha gama and beta
- GTP to GDP
- inactive
- active
- high
1.the activity status of G protein is determined by the — subunit
2. – families of G alpha proteins based on — similarities these are:
3. the main purpose of G protein is to — amplifier or — protein activity
- alpha
- 4
- structural
- Gas , Gai , Gaq , Ga12
- regulate
- effector
beta and gamma exist as — and have – enzymayic activity
- we have – different b and – different y
- they can also exert — activity
- dimers
- no
- 6
-11 - signilliging
mechanism of action of the GPCR:
1.——
- the alpha and gamma of G proteins anchor it to the membrane in an — state
- the G protein is not linked to the —
- G protein has —–
2. —–
- receptor ligand binds to —-
- the occupied receptor couples w the —-
- GDP is replaced w —
3. —–
- alpha-gtp is the — form of the receptor
- alpha-gtp complex dissociates from the receptor to interact w the —-
4. activation of —–
—- is an enzyme that generates cAMP and important 2nd messenger in cells
this enzyme can be activated by —– ( b adrenergic receptors ) and its inhibited by —-
-preactivation
- unbound / inactive
- receptor
- GDP -protein
- ligand binding and activation
- GPCR
- alpha subunit
- GTP
- signal generation
- active
- effector enzyme
- adenylate cyclase
- adenylate cyclase
- GPCR ( b adrenegenic receptors , G alpha s )
- alpha adrenegnic receptors
-
— activates protein kinases
cAMP
cAMP-dependetn kinases have many substrate as:
cAMP is metabolised by —–
- substrates include: ion channels and metabolic pathways
- phosphodiesterase ( from cAMP to AMP )
G alpha s activares —– and is inhibited by —-
adenyl cyclase , G alpha i ( inhibited by pertussis toxin whopping cough )
the GTPase activity of the alpha subunit is —- when the effector protein Is bound which causes hydrolysis of ——-
the GDP-bound alpha subunit reunites w the — complex
- increased
- GTP to GDP
- By complex
( this is how the GPCR is switched off )
regulatory control of GPCR :
1. —- ligand bound receptor acts GEF and accelerates signalling
2. —– By acts as GDI preventing GDP release which inhibits signalling
3. —– stimulates GTPase activity and turn off signalling
- guanine nucelotide exchange factors ( GEF )
- guanine nucleotide dissociation inhibitor ( GDI )
- GTPase accelerating proteins ( GAPs)
when adenylate cyclase activity is disrupted:
—- aka travellers diarrhoea
— modification of G alpha s and cant hydrolyse —- ( locked on )
- elevated cAMP levels in colonic epithelium cause —- of water and ions
- it leads to:
- treatment includes:
- e coli toxins
- covenant
- gtp
- efflux
- severe diarrhoea and dehydration
1. loperamide/imodium acts as an opioid receptor agonist in large intestine
2. treatment : opiate receptor coupled to Gi
3. through Gi opium antagonises the out of control Gs
activation of phopsholidser c by the GPCR signalling:
- an —– activated effector protein and classically activated by —-
—- phosphoinositide PIP from the membrane
produces second messengers:
- alternative g protein
- G alpha q
- hydrolysis
- DAG and inositol triphosphate IP3
—– is soluble in water and binds to the IPS receptor in er
results in — release for smooth muscle contraction , hormone release and neurone transmitter release . the signal terminated by —- of terminal phosphate
- IP3
- Ca+2
- removal
— lipid soluble and activates protein kinase c ( PKC ) in the membrane
there are at least — types of PKU and have many physiological function
- DAG
- 6
summary:
1. g coupeled receptors are linked to —–
2. g coupled proteins can generate varied and complex — cascade
3. —– enzymes targets by activated g protein include: adenylate cyclase and phospholipase c
4. adenylate cyclase and phospholipase c activity differentially regulated by different —–
- hetrotrimetric G proteins
- signalling
- classical effectors enzymes
- G protein c activity
