CBG31 Flashcards
4 receptor types and examples?
ionotrophic -Nicotinic ACh receptor
metabotrophic -. Muscarinic ACh receptor
tyrosin kinase-growth factors: EGF
nuclear receptors-Steroid hormones
explain the 4 receptor tyes and what they are?
Ionotropic receptors – integral ion channel
Metabotropic receptors -protein coupled
Tyrosine kinase receptors – tyrosine autophosphorylation
Nuclear receptors – DNA binding and transcription
why was nAChR the first ligand-gated receptor protein to be purified chemically and studied electrophysiologically?
1)abundance in ELECTROPLAX ORGAN of teleosts 1kg has over 100mg of receptor
2)nAChRs re sensitive to
a-bungarotoxin (a-BuTX)a component of cobra venom. Useful in electrophysiological and biochemical study
where are nicotine acetylcholine receptors found?
at neuromuscular junction
Nicotinic ACh receptor structure
have 5 protein subunits 2 alpha 2 beta 1 gamma (middle) to orm a transmembrane channel
and the alpha subunits contain the sites that bind ach. The negatively chargd internal potion bears selectivity filter for Na+ and K+.
how Nicotonici ACh eceptor works?
ligand gated channel
exists in 3 functional states.
resting ( closed)
activated (open)
Desensitizd( closed but with ach stil bound)
2 ACh molecules bind and cause the channel to open, Channel can flick between resting (closed) and activated. 2 molecules unbinding causes closue. 1ms after opning the channel may also desensitize.
what are other tyes of ligand gated (integral ion channels) are there?
GABA and Glycine–> also fast resonse,
thought to have common ncestral oigin as have pentameric structure
ach composed of 2-4 subunits and like AchR only 1 subunit typ binds to the agonist
what subunits bind to Ach?
alpha subunits
what is a 7 transmembrane receptor that interacts with G proteins?
Muscuranuc Ach receptor–> metabotropic recpotor that is G coupled protein receptor.
what is the muscarinic acetylcholine ceptor structure?
460 aa and is 70KDa, is 7 transmembrane receptor.
at least 5 different recptors exist M1-M5
what segments are involved in g protein activation?
The cytoplasmic end of segment III and the intracellular loops I2 and I3
Explain what happens to the muscarenic rector in order or potassium to flow through.
Ach binds to receptor and receptor causes conformational change that interacts with G protein and affects alpha and beta subunit leading to activation.Th alpha
subunit nds up gaining ATP and separats of fom the rest of th g potein. This alpha subunit then binds to the K+ channel and opens the K+ channel.
what are examples o secondary messengers other g coupled receptors use?
second messengers e.g. IP3, cAMP, cGMP
what can toxins do to G proteins? give exampls
peristasis- inhibits
cholatoxin-activates
harmful as bind leading to complete inactivation or activation
explain alpha molcule in muscaranic receptor? whta is its resting state?
resting stat=GDP bound
the acetylco A binds, GD eleased,GT changes to G potein confomation and alpha subunit beaks away
receptor antagonist
receptor/ligand/ drug that dampons antagonist mediated responses
what are secondary messengers?
molecules that relay signals eceived at ecptor on cell surface ie arival o protein hormones or growth factors –> target molecules
RELAY
and AMLIFY the signal strength
NAme 5 neurotransmittrs
Acetylcholine Dopamine GABA gamma aminobutyric acid Glycine Glutamate
what does the effect of the neurotransmitter usually rely on?
properties of the postsynatic cell
what doe ach show in terms of excitation and inhibition?
interestingly can do both
what does dopamine show wrt location?
different actions,in different neurons
effect differs with location
criteria to be met by candidateneurotransmitter?
1) SAME PHYSIOLOGICAL EFFECTS -when applied to postynatic membrane must have same physiological effects in postsynaptic cell as presynatic stimulation
2) must be RELEASED DURING ACTIVITY of presynatic neurone
3) action of the substance must BE BLOCKD by the same agents which block natural transmission at the synapse
explain how the tyrosine kinase receptor is activatd?
1) signal dimer (e.gAGF) binds
2) kinase activity is stimulated
3) tyrosine kinase domain is phoshorytlated
4) this leads to intracellular proteins binding to phospho-tyrosin docking sites e.g(P13K,PLCgamma)
what ar PI3K and LCy examle of?
intracellular proteins (tyrosine kinase)
how does the nuclear receptor work?
1) The steroid hormone passes across the plasma membrane
2) it binds to the receptor
3) is shuttled to the gene
4) here it activates transcription and subsequently translation of a new protein.
what is the structural organization of nuclear recetors?
N-teminal domain DNA binding domain (DBD) Hinge egion Ligand binding domain C-terminal domain
how many sections of dna organisation in nuclear receptors?
5
N-terminal regulatory domain
Contains the activation function 1 (AF-1) whose action is independent of the presence of ligand
DNA-binding domain (DBD
Highly conserved domain containing two zinc fingers that binds to specific sequences of DNA called hormone response elements (HRE).
Hinge region:
Thought to be a flexible domain that connects the DBD with the LBD. Influences intracellular trafficking and subcellular distribution.
Ligand binding domain (LBD):
Moderately conserved in sequence and highly conserved in structure between the various nuclear receptors. The LBD also contains the activation function 2 (AF-2) whose action is dependent on the presence of bound ligand.
C-terminal domain:
Highly variable in sequence between various nuclear receptors
