Sandbox Reserved 1723: Difference between revisions

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==== ''PIF Motif'' ====

MRGPRX2 also differs from typical Class A GPCRs based on substitutions in the PIF/connector motif, which acts as a microswitch. PIF plays a role in connecting the binding pocket to conformational rearrangements required for receptor activation<ref name="Schonegge">Schonegge, Anne-Marie, et al. "Evolutionary action and structural basis of the allosteric switch controlling β2AR functional selectivity." Nature, Nature Publishing Group, 18 December 2017, https://www.nature.com/articles/s41467-017-02257-x</ref>. The PIF motif is located towards the base of the TM domains. In a Class A GPCR, like <scene name='90/904327/B2arpif_pt_2/1'>β2AR, the PIF motif</scene> consists of Phe-211, Ile-121, and Phe-282 on TM domains 5, 3, and 6, respectively. However, for <scene name='90/904327/Mxpifnolabel_pt_3/1'>MRGPRX2, this PIF motif~~</scene> <scene name='90/904328/Mxpifnolabel_pt_3/2'>Text To Be Displayed~~</scene> is replaced with Leu-194 on TM5, Leu-117 on TM3, and Phe-232 on TM6. These modifications result in tighter packing around the base of the receptor, indicating slightly different interactions with the intracellular [https://en.wikipedia.org/wiki/G_protein G-proteins].

MRGPRX2 also differs from typical Class A GPCRs based on substitutions in the PIF/connector motif, which acts as a microswitch. PIF plays a role in connecting the binding pocket to conformational rearrangements required for receptor activation<ref name="Schonegge">Schonegge, Anne-Marie, et al. "Evolutionary action and structural basis of the allosteric switch controlling β2AR functional selectivity." Nature, Nature Publishing Group, 18 December 2017, https://www.nature.com/articles/s41467-017-02257-x</ref>. The PIF motif is located towards the base of the TM domains. In a Class A GPCR, like <scene name='90/904327/B2arpif_pt_2/1'>β2AR, the PIF motif</scene> consists of Phe-211, Ile-121, and Phe-282 on TM domains 5, 3, and 6, respectively. However, for <scene name='90/904327/Mxpifnolabel_pt_3/1'>MRGPRX2, this PIF motif</scene> is replaced with Leu-194 on TM5, Leu-117 on TM3, and Phe-232 on TM6. These modifications result in tighter packing around the base of the receptor, indicating slightly different interactions with the intracellular [https://en.wikipedia.org/wiki/G_protein G-proteins].

[[Image:LabeledDRY.PNG|250px|right|thumb|'''Figure 2''': DRY Motif of MRGPRX2 [https://www.rcsb.org/structure/7S8L 7S8L] <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>]]

Sandbox Reserved 1723: Difference between revisions

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 ==== ''PIF Motif'' ====
-MRGPRX2 also differs from typical Class A GPCRs based on substitutions in the PIF/connector motif, which acts as a microswitch. PIF plays a role in connecting the binding pocket to conformational rearrangements required for receptor activation<ref name="Schonegge">Schonegge, Anne-Marie, et al. "Evolutionary action and structural basis of the allosteric switch controlling β2AR functional selectivity." Nature, Nature Publishing Group, 18 December 2017, https://www.nature.com/articles/s41467-017-02257-x</ref>. The PIF motif is located towards the base of the TM domains. In a Class A GPCR, like <scene name='90/904327/B2arpif_pt_2/1'>β2AR, the PIF motif</scene> consists of Phe-211, Ile-121, and Phe-282 on TM domains 5, 3, and 6, respectively. However, for <scene name='90/904327/Mxpifnolabel_pt_3/1'>MRGPRX2, this PIF motif</scene> <scene name='90/904328/Mxpifnolabel_pt_3/2'>Text To Be Displayed</scene> is replaced with Leu-194 on TM5, Leu-117 on TM3, and Phe-232 on TM6. These modifications result in tighter packing around the base of the receptor, indicating slightly different interactions with the intracellular [https://en.wikipedia.org/wiki/G_protein G-proteins].
+MRGPRX2 also differs from typical Class A GPCRs based on substitutions in the PIF/connector motif, which acts as a microswitch. PIF plays a role in connecting the binding pocket to conformational rearrangements required for receptor activation<ref name="Schonegge">Schonegge, Anne-Marie, et al. "Evolutionary action and structural basis of the allosteric switch controlling β2AR functional selectivity." Nature, Nature Publishing Group, 18 December 2017, https://www.nature.com/articles/s41467-017-02257-x</ref>. The PIF motif is located towards the base of the TM domains. In a Class A GPCR, like <scene name='90/904327/B2arpif_pt_2/1'>β2AR, the PIF motif</scene> consists of Phe-211, Ile-121, and Phe-282 on TM domains 5, 3, and 6, respectively. However, for <scene name='90/904327/Mxpifnolabel_pt_3/1'>MRGPRX2, this PIF motif</scene> is replaced with Leu-194 on TM5, Leu-117 on TM3, and Phe-232 on TM6. These modifications result in tighter packing around the base of the receptor, indicating slightly different interactions with the intracellular [https://en.wikipedia.org/wiki/G_protein G-proteins].
 [[Image:LabeledDRY.PNG|250px|right|thumb|'''Figure 2''': DRY Motif of MRGPRX2 [https://www.rcsb.org/structure/7S8L 7S8L] <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>]]