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Many signalling cascades use seven-helical transmembrane receptors coupled to heterotrimeric G proteins (G alpha beta gamma) to convert extracellular signals into intracellular responses. Upon nucleotide exchange catalysed by activated receptors, heterotrimers dissociate into GTP-bound G alpha subunits and G beta gamma dimers, either of which can modulate(More)
Heterotrimeric G proteins have a crucial role as molecular switches in signal transduction pathways mediated by G-protein-coupled receptors. Extracellular stimuli activate these receptors, which then catalyse GTP-GDP exchange on the G protein alpha-subunit. The complex series of interactions and conformational changes that connect agonist binding to G(More)
The structure of a heterotrimeric G protein reveals the mechanism of the nucleotide-dependent engagement of the alpha and beta gamma subunits that regulates their interaction with receptor and effector molecules. The interaction involves two distinct interfaces and dramatically alters the conformation of the alpha but not of the beta gamma subunits. The(More)
Parkinson disease is a neurodegenerative disorder whose symptoms are caused by the loss of dopaminergic neurons innervating the striatum. As striatal dopamine levels fall, striatal acetylcholine release rises, exacerbating motor symptoms. This adaptation is commonly attributed to the loss of interneuronal regulation by inhibitory D(2) dopamine receptors.(More)
  • H E Hamm
  • 1998
A large number of hormones, neurotransmitters, chemokines, local mediators, and sensory stimuli exert their effects on cells and organisms by binding to G protein-coupled receptors. More than a thousand such receptors are known, and more are being discovered all the time. Heterotrimeric G proteins transduce ligand binding to these receptors into(More)
Aluminium fluoride (AIF-4) activates members of the heterotrimeric G-protein (G alpha beta gamma) family by binding to inactive G alpha.GDP near the site occupied by the gamma-phosphate in G alpha.GTP (ref. 3). Here we describe the crystal structure of transducin alpha.GDP activated with aluminium fluoride (Gt alpha.GDP.AIF-4.H2O) at 1.7 A, a resolution(More)
Both the ␣ and ␤␥ subunits of heterotrimeric guanine nucleotide–binding proteins (G proteins) communicate signals from receptors to effectors. G␤␥ subunits can regulate a diverse array of effectors, including ion channels and enzymes. G␣ subunits bound to guanine diphosphate (G␣-GDP) inhibit signal transduction through G␤␥ subunits, suggesting a common(More)
In multicellular organisms from Caenorhabditis elegans to Homo sapiens, the maintenance of homeostasis is dependent on the continual flow and processing of information through a complex network of cells. Moreover, in order for the organism to respond to an ever-changing environment, intercellular signals must be transduced, amplified, and ultimately(More)
The molecular interfaces between Gs and the beta-adrenergic receptor were investigated using synthetic peptides corresponding to various regions of its alpha subunit, alpha s. These experiments were carried out on saponin-permeable C6 glioma cells in which the beta-adrenergic receptor appears tightly coupled to Gs. Synthetic site-specific peptides from(More)
The interaction between receptors and guanine nucleotide binding (G) proteins leads to G protein activation and subsequent regulation of effector enzymes. The molecular basis of receptor-G protein interaction has been examined by using the ability of the G protein from rods (transducin) to cause a conformational change in rhodopsin as an assay. Synthetic(More)