CBG31

Question 1

4 receptor types and examples?

Answer 1

ionotrophic -Nicotinic ACh receptor

metabotrophic -. Muscarinic ACh receptor

tyrosin kinase-growth factors: EGF

nuclear receptors-Steroid hormones

Question 2

explain the 4 receptor tyes and what they are?

Answer 2

Ionotropic receptors – integral ion channel

Metabotropic receptors -protein coupled

Tyrosine kinase receptors – tyrosine autophosphorylation

Nuclear receptors – DNA binding and transcription

Question 3

why was nAChR the first ligand-gated receptor protein to be purified chemically and studied electrophysiologically?

Answer 3

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

Question 4

where are nicotine acetylcholine receptors found?

Answer 4

at neuromuscular junction

Question 5

Nicotinic ACh receptor structure

Answer 5

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+.

Question 6

how Nicotonici ACh eceptor works?

Answer 6

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.

Question 7

what are other tyes of ligand gated (integral ion channels) are there?

Answer 7

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

Question 8

what subunits bind to Ach?

Answer 8

alpha subunits

Question 9

what is a 7 transmembrane receptor that interacts with G proteins?

Answer 9

Muscuranuc Ach receptor–> metabotropic recpotor that is G coupled protein receptor.

Question 10

what is the muscarinic acetylcholine ceptor structure?

Answer 10

460 aa and is 70KDa, is 7 transmembrane receptor.

at least 5 different recptors exist M1-M5

Question 11

what segments are involved in g protein activation?

Answer 11

The cytoplasmic end of segment III and the intracellular loops I2 and I3

Question 12

Explain what happens to the muscarenic rector in order or potassium to flow through.

Answer 12

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.

Question 13

what are examples o secondary messengers other g coupled receptors use?

Answer 13

second messengers e.g. IP3, cAMP, cGMP

Question 14

what can toxins do to G proteins? give exampls

Answer 14

peristasis- inhibits
cholatoxin-activates

harmful as bind leading to complete inactivation or activation

Question 15

explain alpha molcule in muscaranic receptor? whta is its resting state?

Answer 15

resting stat=GDP bound

the acetylco A binds, GD eleased,GT changes to G potein confomation and alpha subunit beaks away

Question 16

receptor antagonist

Answer 16

receptor/ligand/ drug that dampons antagonist mediated responses

Question 17

what are secondary messengers?

Answer 17

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

Question 18

NAme 5 neurotransmittrs

Answer 18

Acetylcholine
Dopamine
GABA gamma aminobutyric acid
Glycine
Glutamate

Question 19

what does the effect of the neurotransmitter usually rely on?

Answer 19

properties of the postsynatic cell

Question 20

what doe ach show in terms of excitation and inhibition?

Answer 20

interestingly can do both

Question 21

what does dopamine show wrt location?

Answer 21

different actions,in different neurons

effect differs with location

Question 22

criteria to be met by candidateneurotransmitter?

Answer 22

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

Question 23

explain how the tyrosine kinase receptor is activatd?

Answer 23

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)

Question 24

what ar PI3K and LCy examle of?

Answer 24

intracellular proteins
(tyrosine kinase)

Question 25

how does the nuclear receptor work?

Answer 25

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.

Question 26

what is the structural organization of nuclear recetors?

Answer 26

N-teminal domain
DNA binding domain (DBD)
Hinge egion
Ligand binding domain
C-terminal domain

Question 27

how many sections of dna organisation in nuclear receptors?

Answer 27

5

Question 28

N-terminal regulatory domain

Answer 28

Contains the activation function 1 (AF-1) whose action is independent of the presence of ligand

Question 29

DNA-binding domain (DBD

Answer 29

Highly conserved domain containing two zinc fingers that binds to specific sequences of DNA called hormone response elements (HRE).

Question 30

Hinge region:

Answer 30

Thought to be a flexible domain that connects the DBD with the LBD. Influences intracellular trafficking and subcellular distribution.

Question 31

Ligand binding domain (LBD):

Answer 31

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.

Question 32

C-terminal domain:

Answer 32

Highly variable in sequence between various nuclear receptors