Search results for "GPCR"

NMR Investigation of Structures of G-Protein Coupled Receptor Folding Intermediates

2016

Folding of G-protein coupled receptors (GPCRs) according to the two-stage model (Popot, J. L., and Engelman, D. M. (1990) Biochemistry 29, 4031-4037) is postulated to proceed in 2 steps: partitioning of the polypeptide into the membrane followed by diffusion until native contacts are formed. Herein we investigate conformational preferences of fragments of the yeast Ste2p receptor using NMR. Constructs comprising the first, the first two, and the first three transmembrane (TM) segments, as well as a construct comprising TM1-TM2 covalently linked to TM7 were examined. We observed that the isolated TM1 does not form a stable helix nor does it integrate well into the micelle. TM1 is significant…

Identification of GPR23/LPA4 as a candidate G protein-coupled receptor for Guanosine

2012

G protein biased signaling by non-catechol dopamine D1 receptor agonists

2020

Dopamine is a catecholamine neurotransmitter with essential roles in voluntary movement, working memory, attention, and reward. Dopamine acts through five G protein coupled receptors with the D1 and D5 receptors (D1R) stimulating Galphas/olf activation and increasing neuronal excitability. Deficits in D1R signaling are implicated in Parkinson’s disease motor deficits as well as cognitive deficits in schizophrenia and attention deficit hyperactivity disorder. For more than 40 years, academic and industry scientists have been searching for a drug-like D1R agonist, but this has remained elusive. The challenge in developing D1R selective agonists is that all previous agonists possess a common p…

Pharmacological comparison of rat and human melanocortin 3 and 4 receptors in vitro.

2002

Abstract The melanocortin 3 and 4 receptors are G-protein-coupled receptors found in the hypothalamus with important role in regulation of the energy balance. In this study, we performed pharmacological comparison of the rat and human melancortin (MC) 3 and MC4 receptors. We transiently expressed the genes for these receptors individually in a mammalian cell line and determined the binding affinities to several MSH peptides. The results showed no major difference between the rat and human MC3 receptors while the rat MC4 receptor had higher affinity to several peptides compared with the human MC4 receptor. NDP-, α-, β-, γ-MSH, ACTH(1–24), HS014 and MTII had from 5- to 34-fold higher affinity…

Origin of neuronal-like receptors in Metazoa: cloning of a metabotropic glutamate/GABA-like receptor from the marine sponge Geodia cydonium.

1999

To date, no conclusive evidence has been presented for the existence of neuronal-like elements in Porifera (sponges). In the present study, isolated cells from the marine sponge Geodia cydonium are shown to react to the excitatory amino acid glutamate with an increase in the concentration of intracellular calcium [Ca2+]i. This effect can also be observed when the compounds L-quisqualic acid (L-QA) or L-(+)-2-amino-4-phosphonobutyric acid (L-AP-4) are used. The effect of L-QA and L-AP-4, both agonists for metabotropic glutamate receptors (mGluRs), can be abolished by the antagonist of group I mGluRs, (RS)-alpha-methyl-4-carboxyphenylglycine. These data suggest that sponge cells contain an mG…

An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling

2017

Signaling receptors dynamically exit cilia upon activation of signaling pathways such as Hedgehog. Here, we find that when activated G protein-coupled receptors (GPCRs) fail to undergo BBSome-mediated retrieval from cilia back into the cell, these GPCRs concentrate into membranous buds at the tips of cilia before release into extracellular vesicles named ectosomes. Unexpectedly, actin and the actin regulators drebrin and myosin 6 mediate ectosome release from the tip of cilia. Mirroring signal-dependent retrieval, signal-dependent ectocytosis is a selective and effective process that removes activated signaling molecules from cilia. Congruently, ectocytosis compensates for BBSome defects as…

Mitochondrial DNA deletion and male infertility

2009

Abstract The term “male infertility” does not constitute a defined clinical syndrome, but rather, a collection of different conditions exhibiting a variety of aetiologies and varying diagnosis. In men, oligozoospermia, asthenozoospermia, teratozoospermia and azoospermia are the main causes of infertility. The present research is aimed to investigate if mtDNA deletions can cause sperm defects in idiopathic astenozoospermic patients with different sperm motility and sperm concentration. The incidence of deletions in mtDNA (mtDNA) was co-related with diagnostic categorization of male infertility when 6.6kb out of the 16.6kb of the mitochondrial genome was amplified from whole sperm samples, f…

Expression and characterization of the human sweet taste receptor expressed in a mammalian inducible cell line

2018

International audience; Sweet taste perception is mediated by a heterodimeric receptor composed of the two distinct protein subunits, TAS1R2 and TAS1R3. TAS1R2 and TAS1R3 subunits are members of the small family of class C GPCRs. Class C GPCRs share a large N-terminal domain (NTD) linked to the heptahelical transmembrane domain by a cysteine-rich region. TAS1R2/TAS1R3 is the primary receptor for a diverse range of sweet compounds including natural sugars, sweet amino acids, artificial sweeteners and plant sweet-tasting proteins. In order to understand the molecular mechanisms that govern receptor – ligand interactions and the relative contribution of the two subunits to the detection of swe…

Interactions between cholinergic and fibroblast growth factor receptors in brain trophism and plasticity

2014

Acetylcholine, acting on both nicotinic receptors (nAChRs) and muscarinic receptors (mAChRs), plays a role in the regulation of synaptic plasticity, being involved in the regulation of cellular processes and cognitive functions, such as learning, memory and attention. Recently, G protein coupled receptors (GPCRs), including mAChRs, have been reported to transactivate tyrosine-kinase receptors (RTK), such as epidermal growth factor receptor (EGFR), and initiate their intracellular signaling. In this minireview we have first analysed the RTK transactivation mechanisms, involving cholinergic receptors, and thereafter the interplay between AChR and neurotrophic factor systems built up by FGF2 a…

The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition

2018

International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …