ArticleThe Journal of biological chemistry2016
A Conserved Hydrophobic Core in Gαi1 Regulates G Protein Activation and Release from Activated Receptor.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Ligand-dependent G protein dynamics underlying opioid efficacy.Nature structural & molecular biology · 2026Article
- G protein diffusion states reveal receptor binding dynamics at single-molecule scale.Cell chemical biology · 2026Article
- Pathogenic Gαo Mutants Drive Dominant GPCR Coupling in GNAO1 Encephalopathies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Dominant Gα mutations in human disease: unifying mechanisms and treatment strategies.EMBO molecular medicine · 2025Review
- Ligand-dependent G protein dynamics underlying opioid signaling efficacy.bioRxiv : the preprint server for biology · 2025Article
- Hidden GPCR structural transitions addressed by multiple walker supervised molecular dynamics (mwSuMD).eLife · 2025Article
- A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.Nature communications · 2024Article
- Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.The EMBO journal · 2024Article
- Structural basis of omega-3 fatty acid receptor FFAR4 activation and G protein coupling selectivity.Cell research · 2023Article
- Pathway selectivity in Frizzleds is achieved by conserved micro-switches defining pathway-determining, active conformations.Nature communications · 2023Article
- The role of G protein conformation in receptor-G protein selectivity.Nature chemical biology · 2023Article
- Stickier G-protein conformations.Nature chemical biology · 2023Article
- Structures of Ric-8B in complex with Gα protein folding clients reveal isoform specificity mechanisms.Structure (London, England : 1993) · 2023Article
- The Conformational Dynamics of Heterotrimeric G Proteins During GPCR-Mediated Activation.Sub-cellular biochemistry · 2022Review
- Delineation of molecular determinants for FR900359 inhibition of GThe Journal of biological chemistry · 2020Article
- Ric-8A, a GEF, and a Chaperone for G Protein α-Subunits: Evidence for the Two-Faced Interface.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Article
- Large-scale conformational rearrangement of the α5-helix of Gα subunits in complex with the guanine nucleotide exchange factor Ric8A.The Journal of biological chemistry · 2019Article
- Structural basis for GPCR-independent activation of heterotrimeric Gi proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structural biology of G protein-coupled receptor signaling complexes.Protein science : a publication of the Protein Society · 2019Review
- Combined bioinformatics analysis reveals gene expression and DNA methylation patterns in osteoarthritis.Molecular medicine reports · 2018Article
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 2 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor-mediated heterotrimeric G protein activation is a major mode of signal transduction in the cell. Previously, we and other groups reported that the α5 helix of Gαi1, especially the hydrophobic interactions in this region, plays a key role during nucleotide release and G protein activation. To further investigate the effect of this hydrophobic core, we disrupted it in Gαi1 by inserting 4 alanine amino acids into the α5 helix between residues Gln(333) and Phe(334) (Ins4A). This extends the length of the α5 helix without disturbing the β6-α5 loop interactions. This mutant has high basal nucleotide exchange activity yet no receptor-mediated activation of nucleotide exchange. By using structural approaches, we show that this mutant loses critical hydrophobic interactions, leading to significant rearrangements of side chain residues His(57), Phe(189), Phe(191), and Phe(336); it also disturbs the rotation of the α5 helix and the π-π interaction between His(57) and Phe(189) In addition, the insertion mutant abolishes G protein release from the activated receptor after nucleotide binding. Our biochemical and computational data indicate that the interactions between α5, α1, and β2-β3 are not only vital for GDP release during G protein activation, but they are also necessary for proper GTP binding (or GDP rebinding). Thus, our studies suggest that this hydrophobic interface is critical for accurate rearrangement of the α5 helix for G protein release from the receptor after GTP binding.
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.