What are the primary, secondary, and tertiary structures in the human AT2 receptor that are necessary for G-protein coupling and activation?



Introduction to Angiotensin II Hormone (Ang II)
Angiotensin II octapeptide is a naturally occurring hormone: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe and Sar1Ile8-Angiotensin II is a synthetic version of Angiotension II : Sar-Arg-Val-Tyr-Ile-His-Pro-Ile. They are best known for blood pressure regulation, body fluid homeostasis, and electrolyte balance (AT1R mediated) and also found to influence cell growth, differentiation, and death.

The G-Protein Coupled Receptor(GPCR) Superfamily
All G-protein receptors are homologous, this has become clear from DNA sequencing experiments. The amino acid sequences of a large number of these receptors reveal a common structure consisting of a single polypeptide chain that threads back and forth across the lipid bilayer seven times. Common structural motifs found in all GPCRs include: 1.) Seven a-helical hydrophobic transmembrane regions 2.) Three extracellular loops and tail 3.) Three intracellular loops and tail 4.) A variant of the DRY motif, a highly conserved motif thought to be involved in G-protein coupling.



If a receptor in an active state encounters a G protein, it may activate it. Some evidence suggests that receptors and G proteins are actually pre-coupled. For example, binding of G proteins to receptors affects the receptor's affinity for ligands. Activated G proteins are bound to GTP. Further signal transduction depends on the type of G protein. The enzyme adenylate cyclase is an example of a cellular protein that can be regulated by a G protein, in this case the G protein Gs. Adenylate cyclase activity is activated when it binds to a subunit of the activated G protein (Figure 2, Panel D). Activation of adenylate cyclase ends when the G protein returns to the GDP-bound state.