G-Protein Coupled Receptors
G-protein coupled receptors(GCPRs) are a large family of cell surface membrane proteins. Once bound to a wide variety of extracellular ligands, GCPRs undergo a conformational change and relay information to intracellular secondary messengers [1]. This G protein activation results in a cellular response dependent on the ligand bound and location of the GPCR in the body. GCPRs can be broken down into five families: the rhodopsin family (class A, 701 members), the secretin family (class B, 15 members), the adhesion family (24 members), the glutamate family (class C, 15 members), and the frizzled/taste family (class F, 24 members) [2]. All of the families have a similar transmembrane (TM) domain consisting of seven ɑ-helices complexed with intracellular G proteins.
Class A GCPRs
Class A GPCRS or rhodopsin-like GPCRS are the largest and most studied type of GPCRS. Due to the diversity of these receptors they are found in many aspects of physiology. They are characterized by conserved motifs including DRY, PIF, Sodium Binding, and the CWxP.6 A common example of a class A GPCRS is the β2AR receptor (PDB: 3sn6).
MRGPRs
Structure with
Structure with
The human itch GPCR, or Mas-related G-protein coupled receptor (MRGPR), is a Class A GPCR found in human sensory neurons and is responsible for the sensation of “itching” caused by skin irritation and diseases, insect bites, and hypersensitivity to certain drugs. There are currently four groups consisting of MRGPRX1, MRGPRX2, MRGPRX3, and MRGPRX4. In particular, MRGPRX4 is responsible for cholestatic itch while MRGPRX2 regulates degranulation and hypersensitivity itch reactions [3]. These two, chiefly MRGPRX2, are often targets for drugs that result in mast cell degranulation and hypersensitivity side effects. In comparison to other Class A GPCRs, MRGPRX2 binds to an even wider range of ligands, including agonists such as cations and peptides.
Types of Ligand Bound
Cation
Peptide
Specific Traits
Disulfide bonds
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PIF Motif
DRY Motif
Sodium Binding
MRGPRX2 Signaling Pathway
Function
Conformational Changes
What It Triggers
Clinical Relevance
Drugs
References
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