Further, G protein-coupled receptor 7-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors and is known as (GPLR) G protein-coupled receptors (GPCR), the extracellular sense molecule , constitute a family protein receptor massive, and the cells respond to activation ultimately signaling pathway. Because they pass through seven times the cell membrane, they pass through the cell membrane, they are known as seven-transmembrane receptors, they are referred to as transmembrane receptors.
G protein-coupled receptors are found in eukaryotic organisms, including yeast, animals and choanoflagellates. Ligands that bind to and activate these receptors, photosensitive compound, smell, pheromones, hormones, and is a neurotransmitter, vary in size to a large protein peptide, from small molecules. The G protein-coupled receptors, about 40% of the modern drugs all have been added, and also involved in many diseases. In other words, was awarded to Robert Lefkowitz and Brian Kobilka for their work chemistry 2012 Nobel Prize, “how, essential. In order to understand the function of G protein-coupled receptors”.
There is signal transduction pathways, including the major G-protein-coupled receptors: Two phosphatidylinositol pathway.When signals and ligands cAMP signals roads, may be coupled to the GPCR acts guanine nucleotide exchange factors as (GEF) cause a conformational change in the GPCR can be. By exchanging its bound GDP for GTP Then, GPCR can be activated G proteins involved. Thereafter, in (Gαs, and GTP bound together in G protein Α subunit, the direct α-subunit intracellular signaling proteins in response to Gαi / O that can be separated and β from the γ-subunit or affect target protein function, to Gαq/11, Gα12/13).
GPCR is an integral membrane protein having a transmembrane helix or seven transmembrane domains. Extracellular portion of the receptor may be glycosylated. Further extracellular loop These include cysteine residues that are highly conserved in two to form disulfide bonds to stabilize the structure of the receptor. 7-transmembrane helix several proteins that are similar (channel rhodopsin), among these proteins, GPCR can include ion channels. As with the GPCR, I have a seven transmembrane domains (of AdipoR2 and AdipoR1 of) 2 and adiponectin receptor 1. The AdipoR1 and AdipoR2 of however, not bound to the G protein (ie, N-terminal extracellular C-terminal cytoplasmic) and facing opposition to the GPCR in the film.
Structural model of initial for GPCR is based on the analogy weak their structure bacteriorhodopsin, which is fixed to both the (1AP9) X-ray crystal structure analysis of the base and (PDB 2BRD, 1AT9) electron diffraction. In 2000, the crystal structure of the first mammalian GPCR of (1F88) that bovine rhodopsin is determined. The main function of the seven transmembrane helix has been maintained, but the relative orientation of the helix, differ significantly from those of bacteriorhodopsin. In 2007, (2R4R, 2R4S) was solved the structure of the first GPCR human. This was immediately followed by the high-resolution structure of (2RH1) same receptor. Β2-adrenergic receptor GPCR structure of this man, was very similar to bovine rhodopsin in terms of the relative orientation of the seven-transmembrane helix. However, the structure of the extracellular loops and the second is completely different between the two structures. As a “cap” that covers the top of the ligand binding site, the difference in the structure, based on the structure of rhodopsin, this cycle emphasizes construction of homology models GPCR other difficult.
The structure of the agonist or /, determined.These structure that is also connected to the GPCR, shows how the ligand lead to structural changes in the cytoplasmic side of the receptor to the extracellular portion of the receptor and active. The biggest change is the move to the outside of the cytoplasmic portion of (TM6 and TM5) transmembrane helix of the fifth and sixth. Structure and lively complex with the Gs of β-2 adrenergic receptor, it was confirmed that you are communicating with the cavity Gα has been created by this movement.
Receptors, when it is linked to GEF domain inactive, the heterotrimeric G proteins to α subunit inactive are. Such a “G-protein” you do not have a non-active when it is bound (or guanine nucleotide not) to guanosine reversible two phosphate (GDP) α, γ subunit (Gα, Gγ and Gβ and β It is a trimer, respectively, of) known as, but it is active when it is bound guanosine triphosphate in (GTP). Upon activation of the receptor domain of the GEF, by in turn, to promote the exchange of GDP for GTP molecules allosterically G protein α subunit, activating the G protein. Because I support cell, 10:1 cytoplasm GTP, total GTP exchange is guaranteed. At this time, in order to provide interactions dimers tight Gβγ monomer and Gα-GTP is possible to modulate the activity of cellular proteins in other current subunit of G proteins, separated from the receptor , as well as each other. However, the degree can diffuse them, palmitoylation of Gα, is limited by the presence of molecular glycosyl phosphatidylinositol (GPI) and added to the C-terminus of covalent Gγ. Phosphatidylinositol GPI-linked, the local lipid rafts, also, to some extent, and fixed (for example, Gβγ) All GPI-binding proteins of the plasma membrane, but is composed of a hydrophobic acyl group, two.
By recombination of the dimer Gβγ that is formed by the G protein “rest”, regenerate finally it is inactive GTP → GDP hydrolysis capability, α subunit (GαGDP) slowly, Gα is the month since again binds to the GPCR, and wait for activation. Often, the regulator RGS protein or G protein signaling,, GTP-ase-type activating protein, or the action of other family allosteric modulation of proteins called the GAP is accelerated rate of GTP hydrolysis. In practice, the activation / Lot (e.g. cyclase cyclase) Primary effector proteins are inactivated by reaction with GAP activity having Gα-GTP. Thus, in this early stage of the process, GPCR-initiated signaling, has a capacity of self-closing, for example.