ArticleProceedings of the National Academy of Sciences of the United States of America2001
Mutant G protein alpha subunit activated by Gbeta gamma: a model for receptor activation?
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 78 citations in OpenAlex.
- Article
- Structures of the Rhodopsin-Transducin Complex: Insights into G-Protein Activation.Molecular cell · 2019Article
- The experiences of a biochemist in the evolving world of G protein-dependent signaling.Cellular signalling · 2018Article
- A Conserved Hydrophobic Core in Gαi1 Regulates G Protein Activation and Release from Activated Receptor.The Journal of biological chemistry · 2016Article
- Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.The Journal of biological chemistry · 2015Article
- A conserved phenylalanine as a relay between the α5 helix and the GDP binding region of heterotrimeric Gi protein α subunit.The Journal of biological chemistry · 2014Article
- Implications of non-canonical G-protein signaling for the immune system.Cellular signalling · 2014Review
- Cryptochrome in sponges: a key molecule linking photoreception with phototransduction.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2013Article
- Structural Aspects of GPCR-G Protein Coupling.Toxicological research · 2013Article
- A constitutively active Gα subunit provides insights into the mechanism of G protein activation.Biochemistry · 2012Article
- Recognition in the face of diversity: interactions of heterotrimeric G proteins and G protein-coupled receptor (GPCR) kinases with activated GPCRs.The Journal of biological chemistry · 2011Review
- GoLoco motif proteins binding to Galpha(i1): insights from molecular simulations.Journal of molecular modeling · 2009Article
- Signaling through G protein coupled receptors.Plant signaling & behavior · 2009Review
- Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits.Biochemistry · 2009Article
- Structural determinants involved in the formation and activation of G protein betagamma dimers.Neuro-Signals · 2009Review
- Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2.Structure (London, England : 1993) · 2008Article
- Abscisic acid regulation of guard-cell K+ and anion channels in Gbeta- and RGS-deficient Arabidopsis lines.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- State-selective binding peptides for heterotrimeric G-protein subunits: novel tools for investigating G-protein signaling dynamics.Combinatorial chemistry & high throughput screening · 2008Review
- Evolution of class-specific peptides targeting a hot spot of the Galphas subunit.Journal of molecular biology · 2008Article
- Rapid-mix flow cytometry measurements of subsecond regulation of G protein-coupled receptor ternary complex dynamics by guanine nucleotides.Analytical biochemistry · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
How receptors catalyze exchange of GTP for GDP bound to the Galpha subunit of trimeric G proteins is not known. One proposal is that the receptor uses the G protein's betagamma heterodimer as a lever, tilting it to pull open the guanine nucleotide binding pocket of Galpha. To test this possibility, we designed a mutant Galpha that would bind to betagamma in the tilted conformation. To do so, we excised a helical turn (four residues) from the N-terminal region of alpha(s), the alpha subunit of G(S), the stimulatory regulator of adenylyl cyclase. In the presence, but not in the absence, of transiently expressed beta(1) and gamma(2), this mutant (alpha(s)Delta), markedly stimulated cAMP accumulation. This effect depended on the ability of the coexpressed beta protein to interact normally with the lip of the nucleotide binding pocket of alpha(s)Delta. We substituted alanine for an aspartate in beta(1) that binds to a lysine (K206) in the lip of the alpha subunit's nucleotide binding pocket. Coexpressed with alpha(s)Delta and gamma(2), this mutant, beta(1)-D228A, elevated cAMP much less than did beta(1)-wild type; it did bind to alpha(s)Delta normally, however, as indicated by its unimpaired ability to target alpha(s)Delta to the plasma membrane. We conclude that betagamma can activate alpha(s) and that this effect probably involves both a tilt of betagamma relative to alpha(s) and interaction of beta with the lip of the nucleotide binding pocket. We speculate that receptors use a similar mechanism to activate trimeric G proteins.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.