ArticleProceedings of the National Academy of Sciences of the United States of America2015
The guanine nucleotide exchange factor Ric-8A induces domain separation and Ras domain plasticity in Gαi1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Conserved residues in the Gα interface show subtype specificity in Gβγ coupling.The Journal of biological chemistry · 2026Article
- Conserved Residues in the Gα interface show subtype specificity in Gβγ coupling.bioRxiv : the preprint server for biology · 2026Article
- Article
- Strategies towards Targeting Gαi/s Proteins: Scanning of Protein-Protein Interaction Sites To Overcome Inaccessibility.ChemMedChem · 2021Review
- Structures of Gα Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.Cell reports · 2020Article
- Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1.Nature communications · 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 underpinnings of Ric8A function as a G-protein α-subunit chaperone and guanine-nucleotide exchange factor.Nature communications · 2019Article
- Structure, Function, and Dynamics of the Gα Binding Domain of Ric-8A.Structure (London, England : 1993) · 2019Article
- Dual phosphorylation of Ric-8A enhances its ability to mediate G protein α subunit folding and to stimulate guanine nucleotide exchange.Science signaling · 2018Article
- GProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif.Nature communications · 2017Article
- Article
- Regulation, Signaling, and Physiological Functions of G-Proteins.Journal of molecular biology · 2016Review
- Nanosecond Dynamics of Gαi1 Bound to Nucleotides or Ric-8A, a Gα Chaperone with GEF Activity.Biophysical journal · 2016Article
- Invited review: Activation of G proteins by GTP and the mechanism of Gα-catalyzed GTP hydrolysis.Biopolymers · 2016Review
- A Model for Direction Sensing in Dictyostelium discoideum: Ras Activity and Symmetry Breaking Driven by a Gβγ-Mediated, Gα2-Ric8 -- Dependent Signal Transduction Network.PLoS computational biology · 2016Article
- SIGNAL TRANSDUCTION. Structural basis for nucleotide exchange in heterotrimeric G proteins.Science (New York, N.Y.) · 2015Article
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Authors and funding
4 authors.
Funding
Abstract
Heterotrimeric G proteins are activated by exchange of GDP for GTP at the G protein alpha subunit (Gα), most notably by G protein-coupled transmembrane receptors. Ric-8A is a soluble cytoplasmic protein essential for embryonic development that acts as both a guanine nucleotide exchange factor (GEF) and a chaperone for Gα subunits of the i, q, and 12/13 classes. Previous studies demonstrated that Ric-8A stabilizes a dynamically disordered state of nucleotide-free Gα as the catalytic intermediate for nucleotide exchange, but no information was obtained on the structures involved or the magnitude of the structural fluctuations. In the present study, site-directed spin labeling (SDSL) together with double electron-electron resonance (DEER) spectroscopy is used to provide global distance constraints that identify discrete members of a conformational ensemble in the Gαi1:Ric-8A complex and the magnitude of structural differences between them. In the complex, the helical and Ras-like nucleotide-binding domains of Gαi1 pivot apart to occupy multiple resolved states with displacements as large as 25 Å. The domain displacement appears to be distinct from that observed in Gαs upon binding of Gs to the β2 adrenergic receptor. Moreover, the Ras-like domain exhibits structural plasticity within and around the nucleotide-binding cavity, and the switch I and switch II regions, which are known to adopt different conformations in the GDP- and GTP-bound states of Gα, undergo structural rearrangements. Collectively, the data show that Ric-8A induces a conformationally heterogeneous state of Gαi and provide insight into the mechanism of action of a nonreceptor Gα GEF.
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