Question

Multiple Can Be Correct. All of the following are correct about G protein-coupled receptors(GPCR) EXCEPT:

After agonist-induced activation, GPCRs are NOT desensitized.

GPCRs contain 7 hydrophobic regions thought to represent their transmembrane domains.

You can sometimes demonstrate that a receptor is coupled to a G protein by using pertussis toxin or cholera toxin.

The target proteins for approximately 40-50% of the drugs on the market are GPCRs.

GPCRs contain multiple serine, threonine and tyrosine residues which can be phosphorylated.

Answer 1

correct option: After agonist-induced activation, GPCRs are NOT desensitized.

After activation of GPCR for a prolonged length GPCRs are indeed desensitized. Desensitization is a process whereby excessive activation leads to loss of sensitivity to the agonist. This desensitization process is carried out primarily by two mechanisms that work simultaneously and additively: (1) phosphorylation of GPCRs by GRKs (GPCR kinases) and (2) arrestin mediated uncoupling of phosphorylated GPCR from G protein activation.

ALL the other statements are correct. GPCRs are single molecules with seven transmembrane domains. The seven transmembrane domains contain hydrophobic sequences that traverse the hydrophobic interior of the membrane. The GPCR bind to the G protein when the G protein is in its GTP-bound form and detaches from it when GTPase activity of the G protein itself removes the GTP for GDP. Pertussis and Cholera toxins essentially rob the G protein off its GTPase function. Therefore, when GTP-bound G-protein is attached with GPCR, these toxins make them stay forever "switched on". Thus, it can be used as a tool to assess the G-protein binding state of a GPCR. Finally, GPCRs contain multiple phosphorylation sites of serine/threonine, and to a lesser extent tyrosine.