Heterologous desensitization can only occur with receptors that have a closely related protein structures?
Answers
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein–linked receptors (GPLR), constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times.[2]
GPCR
Beta-2-adrenergic-receptor.png
The human beta-2 adrenergic receptor in complex with the partial inverse agonist carazolol.[1]
Identifiers
Symbol
7tm_1
Pfam
PF00001
InterPro
IPR000276
PROSITE
PDOC00210
TCDB
9.A.14
OPM superfamily
6
OPM protein
1gzm
CDD
cd14964
Available protein structures:
Pfam
structures
PDB
RCSB PDB; PDBe; PDBj
PDBsum
structure summary
The seven-transmembrane α-helix structure of a G protein-coupled receptor
G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates,[3] and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins. G protein-coupled receptors are involved in many diseases, and are also the target of approximately 34% of all modern medicinal drugs.[4][5][6]
There are two principal signal transduction pathways involving the G protein-coupled receptors:
the cAMP signal pathway and
the phosphatidylinositol signal pathway.[7]
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs, Gαi/o, Gαq/11, Gα12/13).[8]:1160
GPCRs are an important drug target and approximately 34%[9] of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of