Receptor

About: Receptor is a research topic. Over the lifetime, 159318 publications have been published within this topic receiving 8299881 citations.

Agmatine: an endogenous clonidine-displacing substance in the brain

Abstract: Clonidine, an antihypertensive drug, binds to alpha 2-adrenergic and imidazoline receptors The endogenous ligand for imidazoline receptors may be a clonidine-displacing substance, a small molecule isolated from bovine brain This clonidine-displacing substance was purified and determined by mass spectroscopy to be agmatine (decarboxylated arginine), heretofore not detected in brain Agmatine binds to alpha 2-adrenergic and imidazoline receptors and stimulates release of catecholamines from adrenal chromaffin cells Its biosynthetic enzyme, arginine decarboxylase, is present in brain Agmatine, locally synthesized, is an endogenous agonist at imidazoline receptors, a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter

Fas Preassociation Required for Apoptosis Signaling and Dominant Inhibition by Pathogenic Mutations

Abstract: Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.

Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA.

Abstract: Nuclear receptors are multi-domain transcription factors that bind to DNA elements from which they regulate gene expression. The peroxisome proliferator-activated receptors (PPARs) form heterodimers with the retinoid X receptor (RXR), and PPAR-gamma has been intensively studied as a drug target because of its link to insulin sensitization. Previous structural studies have focused on isolated DNA or ligand-binding segments, with no demonstration of how multiple domains cooperate to modulate receptor properties. Here we present structures of intact PPAR-gamma and RXR-alpha as a heterodimer bound to DNA, ligands and coactivator peptides. PPAR-gamma and RXR-alpha form a non-symmetric complex, allowing the ligand-binding domain (LBD) of PPAR-gamma to contact multiple domains in both proteins. Three interfaces link PPAR-gamma and RXR-alpha, including some that are DNA dependent. The PPAR-gamma LBD cooperates with both DNA-binding domains (DBDs) to enhance response-element binding. The A/B segments are highly dynamic, lacking folded substructures despite their gene-activation properties.

Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells

Abstract: OESTROGENS are more readily accumulated and retained in responsive cells than in cells that are not their targets1. Cytoplasmic macromolecules2 which specifically interact with oestradiol and other steroid hormones seem to mediate transfer of the agonist to the nuclear chromatin, where the complex is believed to promote expression of the phenotypic effects3–6. It is generally assumed that the hormone diffuses passively to “cytoplasmic” receptors which determine the cellular specificity of response7. But some experiments indicate that steroid hormones interact with components of biological membranes and may enter their respective target cells by a membrane-mediated process8–12 which is saturable and temperature-dependent13–17. We have investigated steroid-binding components associated with the plasma membranes of cells isolated from endometrium, liver and intestinal mucosa. Endometrial and liver cells show substantial binding to oestrogen immobilised by covalent linkage to an inert support, while intestinal cells have no such binding sites. The relative quantity of these steroid receptors at the outer surfaces of cells from diverse tissues corresponds well with the capacity of a given cell to accumulate and retain oestrogen.