Flashcards in Membranes and receptors - 7 Deck (26):
What is signal transduction?
A basic process in molecular cell biology involving the conversion of a signal from outside the cell to a functional change within the cell.
What are the three "superfamilies" of cell-surface receptor?
1. Ligand-gated (receptor-operated) ion channels e.g. nAChR
2. Receptors with intrinsic enzymatic activity (receptor tyrosine kinases e.g. insulin receptor)
3. G-protein coupled (7TM) receptors (e.g. mAChR)
How do insulin receptors work?
1. Insulin binds to their alpha-subunits -> conformational change
2. Beta-subunits come closer together and auto-phosphorylate each others' tyosine residues
3. These changes recruit adaptor molecules which then control downstream processes which control blood glucose homeostasis.
What are agonists?
Ligands that bind to the receptor and activate it (leading to intracellular transduction events).
What are antagonists?
Ligands that bind to the receptor but DO NOT ACTIVATE it (block the effects of agonists at the receptor).
Names some beta-2 adrenoceptor agonists which are anti-asthma:
Salbutamol and salmeterol.
Name some u-opioid receptor agonists which are used for analgesia/anaesthesia:
Morphone and fentanyl.
Name some beta-adrenoceptor antagonists which are used to manage hypertension:
Propranolol and atenolol (b1 selective).
Name some D2 dopamine receptor antagonists which are anti-schozophrenic:
Haloperidol and sulpiride.
Gene mutation to which GPCR causes retinitis pigmentosa?
Loss-of-function mutation of Rhodopsin.
Gene mutation to which GPCR causes nephrogenic diabetes insipidus?
Loss-of-function mutation of V2 vasopressin receptor -> polyuria.
Gene mutation to which GPCR causes familial male preocious puberty?
Gain-of-function mutation to the LH receptor.
List some stimuli that GPCRs respond to:
Sensory GPCRs: light, odours and tastes.
Different GPCRs: ions, neurotransmitters, peptide and non-peptide hormones, large glycoproteins.
What type of hormone is glucagon?
What type of hormone is adrenaline?
Catecholamine (group of monamines)
What type of hormone is TSH?
What are the basic structural features that all GPCRs share?
1. Single polypeptide chain (300-1200 aa)
2. 7TM-spanning regions
3. Extra-cellular N-terminal
4. Intracellular C-terminal
Which are the two regions of the GPCR that can be responsible for ligand binding?
For some receptors the ligand-binding site is:
1. Formed by 2-3 of the transmembrane domains
2. The N-terminal region (and other extracellular domains) - most likely for large ligands (but not necessarily).
What governs receptor G-protein selection?
1. Activated GCPRs preferentially interact with specific types of G-protein
2. G-protein alpha- and beta/gamma-subunits interact with specific effector proteins.
What type of G-protein is specific for the GPCR Rhodopsin? What pathway does it activate?
Gt-apha protein. It activates cGMP phosphodiesterase.
What is wooping cough (pertussis)?
Pertussis is a highly contagious bacterial disease (caused by Bordetella pertussis) that causes uncontrollable, violent coughing - which can make it hard to breathe. A deep 'wooping' soudn i s often heard when the patient starts to take a breath.
What are the effects of the cholera toxin on Gs-apha proteins What is the clinical effect of this?
They ADP-ribosylate this Gs-apha protein which causes irreversible activation because it interferes with its GTPase activity, therefore the signal cannot be inactivated. This causes increased levels of cAMP in the gut epithelium which in turn leads to secretion of H2O, Na+, K+, Cl−, and HCO3− into the lumen of the small intestine and rapid dehydration.
What are the effects of the pertussis toxin on Gi-alpha proteins?
They ADP-ribosylate this Gi-alpha protein which causes it to be irreversibly INactivated becuases the Gi-alpha protein can no longer be activated by GPCRs.
List some enzyme effectors activated by G-proteins:
1. Adenylyl cyclase: (ATP->cAMP)
2. Phospholipase C: (PIP2 -> IP3 and DAG)
3. Phosphoinositide 3-kinase (PI3K): (PIP2 -> PIP3)
4. cGMP phosphodiesterase: (cGMP -> 5'-GMP)
List some ion channel effectors of G-proteins:
2. G protein-regulated inwardly-rectifying K+ channels (GIRKs).