3rd Oct - Receptor Diversity

Question 1

What is a receptor?

Answer 1

A molecule inside or on the surface of a cell that binds to a specific substance and causes a consistent physiological effect in the cell

Question 2

What is the pharmacological definition of a receptor?

Answer 2

A specialized protein that specifically recognizes and responds to a single endogenous molecule

Question 3

How do cone snails kill fish?

Answer 3

Release conotoxins which mimic fish insulin causing hypoglycemic shock to prey

Question 4

Describe RTKs

Answer 4

Single TM spanning polypeptides which dimerize on ligand binding

Question 5

How are RTKs activated?

Answer 5

Upon ligand binding they dimerize, causing their C-terms to autophosphorylate on specific tyrosines, which create phospho-tyrosine docking sites for proteins with SH2 domains

Question 6

How many GPCRs have been identified in the human genome?

Answer 6

> 800

Question 7

Outline the structure of a GPCR

Answer 7

Single polypeptide chain about 300-1200 aa
Extracellular N-terminal
Intracellular C-terminal
7TMD

Question 8

What is fexofenadine?

Answer 8

BLOCKBUSTER - An anti-histamine H1 blocker

Question 9

What is Olanzapine?

Answer 9

BLOCK BUSTER - Anti-psychotic, blocks 5HT2 and D1/D2 receptors

Question 10

What is Clopidogrel?

Answer 10

BLOCK BUSTER - Anti-coagulant that blocks the P2Y12 receptor

Question 11

Describe rhodopsin

Answer 11

Contains cystein bridges
Member of the largest subfamily
NH2 terminal tail of rhodopsin contains five distorted strands
Opsin covalently links to 11-cis retinal

Question 12

Evolutionarily why did GPCRs develop?

Answer 12

When organisms needed efficient communication between cells the number of GPCRs jumped C. elegans =1149

Question 13

What is the old classification of GPCRs?

Answer 13

A - specific aas within TM regions contribute to ligand binding site
B - Receptor acitivity modifying proteins selectively interact modifying their pharmacological properties
C -

Question 14

What is the new classification for GPCRs?

Answer 14

G - Glutamate (old c)
R - Rhodopsin (old a)
A - Adhesion
F - Frizzled
S - Secretin (old b)

Question 15

Can GPCRs be dimers?

Answer 15

Yes, beleived that many exist as dimeric or higher order oligomeric structures.

Question 16

What is the evidence that GPCRs can be dimers/oligomers?

Answer 16

Higher weight bands on SDS-PAGE
Co-immunoprecipitation of epitope tagged GPCR monomers
Live cell imaging using FRET
High power microscopy techniques of GPCR arrays

Question 17

Give an example of a heterodimeric GPCR

Answer 17

GABA B - both GABAB1 and GABAB2 subunits are required to make a GABAB receptor