G-protein coupled receptors and steroid hormone receptors

Because Gα also has slow GTP→GDP hydrolysis capability, the inactive form of the α-subunit (Gα-GDP) is eventually regenerated, thus allowing reassociation with a Gβγ dimer to form the "resting" G-protein, which can again bind to a GPCR and await activation. The rate of GTP hydrolysis is often accelerated due to the actions of another family of allosteric modulating proteins called Regulators of G-protein Signaling , or RGS proteins, which are a type of GTPase-Activating Protein , or GAP. In fact, many of the primary effector proteins (., adenylate cyclases ) that become activated/inactivated upon interaction with Gα-GTP also have GAP activity. Thus, even at this early stage in the process, GPCR-initiated signaling has the capacity for self-termination.

In a patient with retinitis pigmentosa (RP44; 613769), Morimura et al. (1999) found a 1-bp insertion in codon gly275 (GGA-to-GGGA) near the 3-prime end of the coding region of the RGR gene. The patient had originally been diagnosed with choroidal sclerosis (see 215500). Both affected sibs were heterozygotes and an unaffected sib was homozygous wildtype. The deceased father was said to have been affected by this apparently dominantly inherited disorder. Morimura et al. (1999) detected no alteration of the other allele in the affected sibs.

The G α subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic activity, allowing it to re-associate with G βγ and starting a new cycle. A group of proteins called Regulator of G protein signalling (RGSs), act as GTPase-activating proteins (GAPs), are specific for G α subunits. These proteins accelerate the hydrolysis of GTP to GDP, thus terminating the transduced signal. In some cases, the effector itself may possess intrinsic GAP activity, which then can help deactivate the pathway. This is true in the case of phospholipase C -beta, which possesses GAP activity within its C-terminal region. This is an alternate form of regulation for the G α subunit. Such G α GAPs do not have catalytic residues (specific amino acid sequences) to activate the G α protein. They work instead by lowering the required activation energy for the reaction to take place. [18]

GPCRdb contains data, diagrams and web tools for G protein-coupled receptors (GPCRs). Users can browse all GPCR crystal structures and the largest collections of receptor mutants. Diagrams can be produced and downloaded to illustrate receptor residues (snake-plot and helix box diagrams) and relationships (phylogenetic trees). Reference (crystal) structure-based sequence alignments take into account helix bulges and constrictions, display statistics of amino acid conservation and have been assigned generic residue numbering for equivalent residues in different receptors. For an overview read the GPCRdb poster , articles or documentation .

G-protein coupled receptors and steroid hormone receptors

g-protein coupled receptors and steroid hormone receptors

GPCRdb contains data, diagrams and web tools for G protein-coupled receptors (GPCRs). Users can browse all GPCR crystal structures and the largest collections of receptor mutants. Diagrams can be produced and downloaded to illustrate receptor residues (snake-plot and helix box diagrams) and relationships (phylogenetic trees). Reference (crystal) structure-based sequence alignments take into account helix bulges and constrictions, display statistics of amino acid conservation and have been assigned generic residue numbering for equivalent residues in different receptors. For an overview read the GPCRdb poster , articles or documentation .

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