BIOC 3310 - G protein

orphan receptor doesn't know what

ligand binds to it????

GPCR common structure

Single protein with 7 transmembrane regions

ion channels have

4 transmembrane domains and 5 subunits.

remember the steps. for example she'll ask what happens in step 1. Know that ligand binds to

G Protein receptor causing conformational change.

2. change allows G protein to

come in (has alpha, beta, gamma)(alpha of G protein has to bind to..)

when ligands comes and binds, conformational change of receptor allows

G protein (3subunits) to bind.

DP attached to alpha and gets converted to GTP, hydrolysis and alpha

separates from beta and gamma.

Gβγ dimers interact with a set of effectors that includes some

Gα effectors such as adenylate cyclase and phospholipase C

alpha subunit breaks off

adenylate cyclase.

Phospholipase are 2 important enzymes. Another enzyme,

ATPase is another effector.

Effector systems: (1) adenylate cyclase, Aloha and beta subunit (or beta and gamma) can

regulate the ion channel.

unit with adenylasecyclase. It hydrolyses ATP which becomes cAMP. cAMP goes on to do other things like

binding to protein kinase A and phosphorylates target proteins

can go and interact with ion channels. Can be related to side effects like dry mouth or sweating more etc of drug side effects. So when take drug, its not due to binding to

receptors but that other side processes effected as well

PIP is a substrate (not secondary substrate). Alpha binds to phospholipase. PIP2 binds to it and

phospholipase C hydrolyzes it and splits it up into DAG and IP3.

DAG binds to protein kinase C which goes on to phosphorylate target proteins

Gαq stimulates phospholipase Cβ (1), which cleaves phosphatidylinositol-bis-phosphate (PIP2) into

two secondary messengers: diacylglycerol (DAG), which remains in the cytoplasmic membrane

Gαq stimulates phospholipase Cβ (1), which cleaves phosphatidylinositol-bis-phosphate (PIP2) into two secondary messengers: diacylglycerol (DAG), which remains in the cytoplasmic membrane and activates protein kinase C (2), and

inositoltriphosphate (IP3), which activates a cognate calcium channel in the ER membrane (3).

IP3 goes to ER and acts as ligand to the

calcium channel. It controls the channels

Adrenergic receptors or adrenoceptors

Ligands

norepinephrine (noradrenaline) and epinephrine (adrenaline)

Pharmacophore includes

catechol

-ethanolamine

the diff between them is only

1 functional group.

isoprenaline is good to differentiate between alpha and beta. If it binds tighter,

kd is lower on B (lower the Kd the tighter it is)

Type of reactions:

MAO (monoamine oxidase) catalyzes

oxidation reaction (bc oxygen was added)

Type of reactions: COMT (catechol O-methyltransferase) catalyzes

methylation reaction

ADH (aldehyde dehydrogenase) catalyzes

oxidation reaction (because you're adding more oxygen)

(Tyrosine) Kinase Linked Receptors - Protein serves dual role -

receptor plus enzyme

(Tyrosine) Kinase Linked Receptors, 4 examples

Insulin Receptors, Epidermal Growth Factor Receptors [EGFR, ErbB1, HER1, Nerve Growth Factor Receptors [NGF], Toll Like Receptors [TLRs]

Ligand-activated transcription factors

1. Messenger crosses membrane

2. Binds to receptor

3. Receptor dimerisation

4. Binds co-activator protein

5. Complex binds to DNA

6. Transcription switched on or off

7. Protein synthesis activated or inhibited