Sandbox Reserved 1723: Difference between revisions
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== MRGPRX2 Signaling Pathway == | == MRGPRX2 Signaling Pathway == | ||
== 1. Binding Pocket == | === 1. Binding Pocket === | ||
MRGPRX2 consists of two binding pockets (seen in Figure 2). Sub-pocket 1 consists of primarily hydrophobic aromatic residues; Phe-170, Trp-243, and Phe-244.<ref name="Yang">Yang, Fan, et al. "Structure, function and pharmacology of human itch receptor complexes." Nature, Nature Publishing Group, 17 November 2021, https://www.nature.com/articles/s41586-021-04077-y</ref> These residues provide stabilization with ligands through stacking. This pocket also contains acidic catalytic residues Asp-184 and Glu-164 that interact with substrates by making ion pairs. Lastly, this pocket is in close proximity with the commonly conserved disulfide bond (formed by Cys-168 and Cys-180) seen in most Class A GPCRs. The second binding pocket forms electrostatic interactions with larger substrates (seen in Figure 2), but is generally less studied.<ref name="Cao"/> | MRGPRX2 consists of two binding pockets (seen in Figure 2). Sub-pocket 1 consists of primarily hydrophobic aromatic residues; Phe-170, Trp-243, and Phe-244.<ref name="Yang">Yang, Fan, et al. "Structure, function and pharmacology of human itch receptor complexes." Nature, Nature Publishing Group, 17 November 2021, https://www.nature.com/articles/s41586-021-04077-y</ref> These residues provide stabilization with ligands through stacking. This pocket also contains acidic catalytic residues Asp-184 and Glu-164 that interact with substrates by making ion pairs. Lastly, this pocket is in close proximity with the commonly conserved disulfide bond (formed by Cys-168 and Cys-180) seen in most Class A GPCRs. The second binding pocket forms electrostatic interactions with larger substrates (seen in Figure 2), but is generally less studied.<ref name="Cao"/> | ||
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== 2. MRGPRX2 interaction with G-Protein == | === 2. MRGPRX2 interaction with G-Protein === | ||
MRGPRX2 interacts with two different types of [https://en.wikipedia.org/wiki/G_protein#:~:text=G%20proteins%2C%20also%20known%20as,a%20cell%20to%20its%20interior. G-proteins], Gi and Gq. When activated these G-proteins will initiate the signal transduction pathway. These G-proteins are composed of 3 subunits; α, β, and γ. | MRGPRX2 interacts with two different types of [https://en.wikipedia.org/wiki/G_protein#:~:text=G%20proteins%2C%20also%20known%20as,a%20cell%20to%20its%20interior. G-proteins], Gi and Gq. When activated these G-proteins will initiate the signal transduction pathway. These G-proteins are composed of 3 subunits; α, β, and γ. | ||
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[[Image:GqGi_with_zincs_snip.PNG|300px|right|thumb|'''Figure 5''': Caption.<ref name="Cao"/>]] | [[Image:GqGi_with_zincs_snip.PNG|300px|right|thumb|'''Figure 5''': Caption.<ref name="Cao"/>]] | ||
== 3.After G-Protein Activation == | === 3.After G-Protein Activation === | ||
MRGPRX2 mediates degranulation of mast cells through interaction with Gq and Gi subunits. Gq activation signals through [https://en.wikipedia.org/wiki/Phospholipase_C Phospholipase C], which catalyzes the cleavage of Phosphatidylinositol bisphosphate into [https://en.wikipedia.org/wiki/Diglyceride diacylglycerol (DAG)] and [https://en.wikipedia.org/wiki/Inositol_trisphosphate inositol trisphosphate (IP3)]. DAG is then able to increase the activity of [https://en.wikipedia.org/wiki/Protein_kinase_C protein kinase C]. IP3 receptor is ligand gated calcium channel on the endoplasmic reticulum (ER), that causes the release of calcium in cytoplasm. Subsequently, this results in muscle contraction and enzyme activation. | MRGPRX2 mediates degranulation of mast cells through interaction with Gq and Gi subunits. Gq activation signals through [https://en.wikipedia.org/wiki/Phospholipase_C Phospholipase C], which catalyzes the cleavage of Phosphatidylinositol bisphosphate into [https://en.wikipedia.org/wiki/Diglyceride diacylglycerol (DAG)] and [https://en.wikipedia.org/wiki/Inositol_trisphosphate inositol trisphosphate (IP3)]. DAG is then able to increase the activity of [https://en.wikipedia.org/wiki/Protein_kinase_C protein kinase C]. IP3 receptor is ligand gated calcium channel on the endoplasmic reticulum (ER), that causes the release of calcium in cytoplasm. Subsequently, this results in muscle contraction and enzyme activation. | ||
