Sandbox Reserved 1701: Difference between revisions

The allosteric sodium site in class A GPCRs has been characterized as important in inactive state GPCR stabilization <ref name="Katritch">PMID:24767681</ref>. Katritch et al <ref name="Katritch">PMID:24767681</ref> describe that class A GPCRs lacking conserved D2.50 and other polar residues within the sodium pocket are typically inactive. The MRGPRX2 <scene name='90/904306/Sodium_site_2/2'>sodium binding site</scene> consists of conserved Asp2.50, or Asp-75, and Gly-116 <scene name='90/904306/Alignment_sodium/1'>compared to 5HT2AR</scene> and to the [https://proteopedia.org/wiki/index.php/Neurotensin_receptor#sodium%20binding%20pocket previously conserved] polar residues in the neurotensin receptor binding pocket such as Ser3.39. Other class A GPCRs demonstrate a larger sodium binding pocket with a higher negative character allowing for a suitable environment for sodium ions to bind. In MRGPRX2, this sodium binding pocket lacks the same amount of <scene name='90/904306/Sodium_site_charge/3'>negative character</scene> with the shift to a glycine residue rather than serine. However, evidence suggests that sodium is still able to bind in X2's sodium binding site even with fewer conserved residues.