Topic
GTP-Binding Protein alpha Subunits
About: GTP-Binding Protein alpha Subunits is a research topic. Over the lifetime, 304 publications have been published within this topic receiving 19915 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: Observations supporting the view that G15 functions may extend further beyond the immune system are highlighted and puzzling aspects of G15 signaling are described that offer a novel perspective in the understanding of its physiological role.
Abstract: Heterotrimeric Gproteinstransducethesignalsof thelargestfamilyof membrane receptors(Gprotein-coupled receptors, GPCRs)hence triggeringthe activationof a wide variety of physiological responses.G15 is a G protein characterized by a numberoffunctional peculiarities that make its signaling exceptional: 1) it cancouple a variety of Gs-, Gi/o-, and Gq-linked receptors to phospholipase C activation; 2) relatively to other G proteins, it is poorly affected by b-arrestin-dependent desensitization, the general mechanism that regulates GPCR function and 3) at the protein level, its expression is only detected in highly specific cell types (hematopoietic and epithelial cells). G15 a-subunit displays unique structural and biochemical properties, and is phylogenetically the most recent and divergent component of the Gaq/11 subfamily. All theseaspectsshed amysteriouslighton G15biologicalrole, which remainssubstantiallyelusive.Thus,far,G15 signaling has been analyzed in the context of hematopoiesis. Here, we highlight observations supporting the view that G15 functions may extend further beyond the immune system. In addition, we describe puzzling aspects of G15 signaling that offer a novel perspective in the understanding of its physiological role.
32 citations
TL;DR: The results lead to the suggestion that Gαq can localize its associated receptors to caveolae domains to enhance their signals, and this work has used fluorescence methods to determine the effect of Caveolae on the physical and functional properties of two GPCRs that have been reported to reside in caveolai.
Abstract: Caveolae are membrane domains that may influence cell signaling by sequestering specific proteins such as G-protein-coupled receptors (GPCRs). While previous reports largely show that Gαq subunits,...
31 citations
TL;DR: In this article, the authors used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin type 1 receptor (CCK1R) bound to the CCK peptide agonist.
Abstract: G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11-GPCR complexes, the Gq-α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from "unwinding" of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs.
31 citations
TL;DR: It is concluded that the trimeric G-protein, Gi2, is required for store-activated Ca2+ inflow in hepatocytes and acts between the release of Ca2- from the endoplasmic reticulum and the receptor-activatedCa2+ channel protein(s) in the plasma membrane.
31 citations
TL;DR: Flow cytometry permits quantiatitive and real-time assessments of protein-protein interactions in complex membrane environments and suggests betagamma contributed essentially all of the binding energy for alpha(i1) interaction with the membrane.
Abstract: The dynamics of G protein heterotrimer complex formation and disassembly in response to nucleotide binding and receptor activation govern the rate of responses to external stimuli. We use a novel flow cytometry approach to study the effects of lipid modification, isoform specificity, lipid environment, and receptor stimulation on the affinity and kinetics of G protein subunit binding. Fluorescein-labeled myristoylated Galpha(i1) (F-alpha(i1)) was used as the ligand bound to Gbetagamma in competition binding studies with differently modified Galpha subunit isoforms. In detergent solutions, the binding affinity of Galpha(i) to betagamma was 2 orders of magnitude higher than for Galpha(o) and Galpha(s) (IC50 of 0.2 nM vs 17 and 27 nM, respectively), while in reconstituted bovine brain lipid vesicles, binding was slightly weaker. The effects of receptor on the G protein complex were assessed in alpha(2A)AR receptor expressing CHO cell membranes into which purified betagamma subunits and F-alpha(i1) were reconstituted. These cell membrane studies led to the following observations: (1) binding of alpha subunit to the betagamma was not enhanced by receptor in the presence or absence of agonist, indicating that betagamma contributed essentially all of the binding energy for alpha(i1) interaction with the membrane; (2) activation of the receptor facilitated GTPgammaS-stimulated detachment of F-alpha(i1) from betagamma and the membrane. Thus flow cytometry permits quantiatitive and real-time assessments of protein-protein interactions in complex membrane environments.
29 citations