GPCR

2022-04-23: reference:

GPCR (G-protein coupled receptor) #

• AKA 7-transmembrane (7TM) receptors, because they pass through the membrane 7 times. Weird.

  • Disulfide bonds stabilize the domains, or at least the first two intracellular loops.
  • ICL-3 determines the class of G-protein that bonds. ICL-2 and C-terminus influence binding in some cases.
  • β-arrestin binding can also just cause internalization of the receptor.

• The C-terminal can be palmitoylated at Cysteine residues, targeting the receptor to lipid rafts.

• Neurotransmitters (sometimes known as ’neuromodulators’ in this context) bind to them, and this influx of ion does:

  • Opens the ion channels directly (fr?)
  • Stimulates the neuroreceptor’s corresponding G-protein subunit, which ultimately changes associated gated membrane channels (but not the same)
    • I guess it makes sense, since it only needs one phosphate; ATP is ultimately supplying it. Wonder what happens with the pyrophosphate though. Nucleoside-diphosphate kinase, probably.

• There are 6 types of GPCRs:

  • Class A/1: Rhodopsin-like
    • The largest group. Within it is dopamine, serotonin, histamine, opioid, amongst others - but not acetylcholine.
  • Class B/2: Secretin receptor family
    • Well it can’t be RTKs:
    • Calcitonin
    • Glucagon
    • GHRH
    • Parathyroid hormone receptor
    • Secretin receptor
  • Class C/3: mGluR/pheromone (and GABA-B)
    • Monoamines and neuropeptides often exhibit this behavior.
  • Class D/4: Fungal mating pheromone receptors
  • Class E/5: cAMP receptors
  • Class F/6: Frizzled/Smoothened

• Disrupting GPCR Complexes with Smart Drug-like Peptides

  • These peptides are derived from the TM domains, designed to target oligomers at the ‘interface level’. However they have a short half life, bioavailability, etc. They talk about CB1-5-HT2A and D21.