GPCR structure

Question 1

Classes A-F of GPCRs

Answer 1

Rhodopsin-like
secretin (and adhesion)
metabotropic glutamate
fungal mating pheromone
cAMP
frizzled/smoothened

Only Rhodopsin, secretin, adhesion, metabotropic glutamate, and frizzled found in mammals

Question 2

structure and examples of Rhodopsin-like GPCRs

Answer 2

720 members (most odorant)

NA, adrenaline, 5HT, histamine receptors, and mAChRs

Adenosine, ADP, ATP, UDP, ADP

Substance P, enkephalin, somatostatin, oxytocin.

Mostly bind at the plane of the plasma membrane

Question 3

Structure and examples of secretin/adhesion

Answer 3

Secretin has 16 members. Mainly peptide hormone receptors, e.g., secretin, glucagon. Binding site at the plasma membrane of the GPCR.

Adhesion family has 33 members. Have large N-terminus. They have autoproteolytic cleavage. They interact with proteins on the surface of other cells.

Question 4

structure of Metabotropic glutamate receptors

Answer 4

22 members. Largest in size of GPCRs. They have a large EC N-terminus domain.
Generally, mGluRs have a large extracellular N-terminus, followed by the seven transmembrane domains that traverse the cell membrane, and an intracellular C-terminus.

Question 5

Obligate heterodimers.

Answer 5

GABAB made up of 2 different subunits GABAB1/2. The GABAB2 subunit allows GABAB1 to transport to the cell surface. GABAB1 has binding site. GABAB2 mediates G-protein coupled signalling. They directly couple through allosteric binding. Facilitate each others functions.

T1R1/T1R3 heterodimers are umami receptors, which are activated by glutamate. Allosteric modulation by 5’-GMP

T1R2/T1R3 are sweet receptors activated by sucrose and artificial sweeteners.

Question 6

Beta2-AR structure (archetypal)

Answer 6

7TM domains. Has EC N-terminus and IC C-terminus. 3 IC and EC loops. Each TM domain has 20-24 AAs (mostly aliphatic).

Question 7

Glycosylation (PTM)

Answer 7

Posttranslational modification which binds carbohydrate to the GPCR. Universal for GPCRs. Attaches to an EC asn residue. This PTM formed in rough ER.

The carbohydrates can be linear or branched, simple or mixed. They form a large portion of the receptor mass. They have role in cell surface and cell-cell recognition

Question 8

Acylation (PTM)

Answer 8

14 or 16 carbon fatty acids attach at the IC cys-terminus. This forms a 4th IC loop, which gives further signalling potential.

Question 9

Phosphorylation (PTM)

Answer 9

Attaches a phosphate group to a ser/thr/tyr/his residue. Attaches IC. It rapidly switches off the protein function.

Question 10

Disulphide bridges (PTM)

Answer 10

-S-S- (formed in ER) attached at cys. Can be IC or EC. It coupled two remote sites/polypeptides.

Helps maintain a quaternary structure for the GPCR.