Sandbox Reserved 1718

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=Introduction=
=Introduction=
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[https://proteopedia.org/wiki/index.php/G_protein-coupled_receptors G protein-coupled receptors] (GPCRs) are the largest class of integral membrane proteins.<ref name="Zhang 2015">DOI 10.14348/molcells.2015.0263</ref> GPCRs<ref name= "Zhang 2015"/><ref>PMID: 20019124</ref> are divided into five families; the [https://proteopedia.org/wiki/index.php/Sandbox_Reserved_895 rhodopsin family (class A)], the [https://proteopedia.org/wiki/index.php/4ers secretin family (class B)], the [https://proteopedia.org/wiki/index.php/6wiv glutamate family (class C)], the [https://proteopedia.org/wiki/index.php/6bd4 frizzled/taste family (class F)], and the [https://en.wikipedia.org/wiki/Adhesion_G_protein-coupled_receptor adhesion family].<ref name= "Zhang 2015"/><ref name= "Zhang 2006"/> All GPCRs contain a similar seven α-helical transmembrane domain <scene name='72/727091/Full_Structure_with_Labels/1'>(TMD)</scene> that undergoes a conformation change once bound to its ligand. This conformational change then transduces a signal to a coupled, heterotrimeric G protein which then dictates whether an intracellular signaling pathway will be initiated or inhibited. The initiation of the intracellular signaling pathway occurs in response to a variety of stimuli such as light, Ca<sup>2+</sup>, peptides, different proteins, and many more stimuli. Ultimately, intracellular signaling [https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor#Physiological_roles accomplishes many interesting physiological roles] accomplishes many interesting physiological roles.<ref name= "Zhang 2015"/><ref name= "Zhang 2006">DOI 10.1371/journal.pcbi.0020013</ref>
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[https://proteopedia.org/wiki/index.php/G_protein-coupled_receptors G protein-coupled receptors] (GPCRs) are the largest class of integral membrane proteins.<ref name="Zhang 2015">DOI 10.14348/molcells.2015.0263</ref> GPCRs<ref name= "Zhang 2015"/><ref>PMID: 20019124</ref> are divided into five families; the [https://proteopedia.org/wiki/index.php/Sandbox_Reserved_895 rhodopsin family (class A)], the [https://proteopedia.org/wiki/index.php/4ers secretin family (class B)], the [https://proteopedia.org/wiki/index.php/6wiv glutamate family (class C)], the [https://proteopedia.org/wiki/index.php/6bd4 frizzled/taste family (class F)], and the [https://en.wikipedia.org/wiki/Adhesion_G_protein-coupled_receptor adhesion family].<ref name= "Zhang 2015"/><ref name= "Zhang 2006"/> All GPCRs contain a similar seven α-helical transmembrane domain <scene name='72/727091/Full_Structure_with_Labels/1'>(TMD)</scene> that undergoes a conformation change once bound to its ligand. This conformational change then transduces a signal to a coupled, heterotrimeric G protein which then dictates whether an intracellular signaling pathway will be initiated or inhibited. The initiation of the intracellular signaling pathway occurs in response to a variety of stimuli such as light, Ca<sup>2+</sup>, peptides, different proteins, and many more stimuli. Ultimately, intracellular signaling [https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor#Physiological_roles accomplishes many interesting physiological roles].<ref name= "Zhang 2015"/><ref name= "Zhang 2006">DOI 10.1371/journal.pcbi.0020013</ref>
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Human Itch G-coupled protein receptors (GPCRs), or Mast cell-related GPCRs (MRGPRX), have been identified as pruritogenic receptors and are found in human sensory neurons, specifically in the connective tissue mast cells and dorsal root ganglia in humans.<ref name= "davidson2011">DOI: 10.1016/j.tins.2010.09.002<ref/> They are classified as class A GPCRs, however, MRGPRX receptors respond to a diverse number of agonists, antagonists, and inverse agonists some of which are not typical ligands of class A receptors. MRGPRX are involved in host defense, pseudo-allergic reactions, non-histaminergic itch, periodontitis, neurogenic inflammation, and inflammatory pain.<ref name= "davidson2011"</ref>
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Human Itch G-coupled protein receptors (GPCRs), or Mast cell-related GPCRs (MRGPRX), have been identified as pruritogenic receptors and are found in human sensory neurons, specifically in the connective tissue mast cells and dorsal root ganglia in humans.<ref name= "davidson2011">DOI: 10.1016/j.tins.2010.09.002</ref> They are classified as class A GPCRs, however, MRGPRX receptors respond to a diverse number of agonists, antagonists, and inverse agonists some of which are not typical ligands of class A receptors. MRGPRX are involved in host defense, pseudo-allergic reactions, non-histaminergic itch, periodontitis, neurogenic inflammation, and inflammatory pain.<ref name= "davidson2011"/>
The determination of the first structures of a ligand-activated GPCR was achieved by Robert J. Lefkowitz and Brian K. Kobilka which won them the 2012 Nobel Prize in Chemistry. They also successfully captured images of the first activated GPCR in a complex with a G protein. See [https://proteopedia.org/wiki/index.php/Nobel_Prizes_for_3D_Molecular_Structure Nobel Prizes for 3D Molecular Structure].
The determination of the first structures of a ligand-activated GPCR was achieved by Robert J. Lefkowitz and Brian K. Kobilka which won them the 2012 Nobel Prize in Chemistry. They also successfully captured images of the first activated GPCR in a complex with a G protein. See [https://proteopedia.org/wiki/index.php/Nobel_Prizes_for_3D_Molecular_Structure Nobel Prizes for 3D Molecular Structure].
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== Related Enzymes ==
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==Related Enzymes==
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Among Human Itch GPCRs, MRGPRX2 is a class A GPCR that regulates mast cell degranulation and itch-related hypersensitivity reactions.<ref name="Can">DOI: 10.1038/s41586-021-04126-6</ref><ref name="Yang"/> MRGPRX2 is also a target of morphinan alkaloids, like morphine, codeine, and dextromethorphan.<ref name="Can"/><ref name="Yang"/> MRGPRX2 couples to nearly all G-protein families and subtypes with robust coupling to G<sub>q</sub> and G<sub>i</sub> families.<ref name="Can"/><ref name="Yang"/>
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Among Human Itch GPCRs, <scene name='90/904324/Mrgprx2_receptor/4'>MRGPRX2</scene> is a class A GPCR that regulates mast cell degranulation and itch-related hypersensitivity reactions.<ref name="Can">DOI: 10.1038/s41586-021-04126-6</ref><ref name="Yang"/> MRGPRX2 is also a target of morphinan alkaloids, like morphine, codeine, and dextromethorphan.<ref name="Can"/><ref name="Yang"/> MRGPRX2 couples to nearly all G-protein families and subtypes with robust coupling to G<sub>q</sub> and G<sub>i</sub> families.<ref name="Can"/><ref name="Yang"/>
<scene name='90/904324/7s8p_mx4/2'>MRGPRX4</scene> is another sub-group of the MRGPRX family, which mediates cholestatic itch and is a target of nateglinide drugs.<ref name="Can"/><ref name="Yang"/> MRGPRX4 also couples to G<sub>q</sub> and G<sub>i</sub> similar to MRGPRX2.
<scene name='90/904324/7s8p_mx4/2'>MRGPRX4</scene> is another sub-group of the MRGPRX family, which mediates cholestatic itch and is a target of nateglinide drugs.<ref name="Can"/><ref name="Yang"/> MRGPRX4 also couples to G<sub>q</sub> and G<sub>i</sub> similar to MRGPRX2.
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*[[Pharmaceutical Drugs]]
*[[Pharmaceutical Drugs]]
*[[Nobel Prizes for 3D Molecular Structure]]
*[[Nobel Prizes for 3D Molecular Structure]]
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*[[Sandbox Reserved 895| Rhodopsin Family GPCRs]]
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*[[4ers| Secretin Family GPCRs]]
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*[[6wiv| Glutamate Family GPCRs]]
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*[[6bd4| Frizzled/Taste Family GPCRs]]
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*[https://en.wikipedia.org/wiki/Adhesion_G_protein-coupled_receptor Adhesion Family GPCRs]

Current revision

Human Itch G-Coupled Protein Receptors

Cryo-EM structure of Gq coupled MRGPRX2.

Drag the structure with the mouse to rotate


Student contributors

Madeline Beck Joey Gareis

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