Evidence map›Paper›PMID 27298341›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding.

David Goricanec, Ralf Stehle, Pascal Egloff, Simina Grigoriu, Andreas Plückthun, Gerhard Wagner, Franz Hagn

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 103 citations in OpenAlex.

  1. Innovative Approach Reveals How Receptors Control G Protein State Equilibria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  6. A deadly taste: linking bitter taste receptors and apoptosis.Apoptosis : an international journal on programmed cell death · 2025
    Review
  7. Article
  8. Stabilization of interdomain closure by a G protein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Article
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  11. Inhibition of adenylyl cyclase by GTPase-deficient GαCell communication and signaling : CCS · 2024
    Article
  12. Review
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  17. Review
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  20. Pituitary Tumorigenesis-Implications for Management.Medicina (Kaunas, Lithuania) · 2023
    Review

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

David GoricanecInstitute for Advanced Study at the Department of Chemistry, Technische Universität München, 85747 Garching, Germany; Center for Integrated Protein Science Munich at the Department of Chemistry, Technische Universität München, 85747 Garching, Germany; Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
Ralf StehleCenter for Integrated Protein Science Munich at the Department of Chemistry, Technische Universität München, 85747 Garching, Germany; Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
Pascal EgloffDepartment of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland;
Simina GrigoriuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Andreas PlückthunDepartment of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland;ORCID 0000-0003-4191-5306
Gerhard WagnerDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 franz.hagn@tum.de gerhard_wagner@hms.harvard.edu.
Franz HagnInstitute for Advanced Study at the Department of Chemistry, Technische Universität München, 85747 Garching, Germany; Center for Integrated Protein Science Munich at the Department of Chemistry, Technische Universität München, 85747 Garching, Germany; Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 franz.hagn@tum.de gerhard_wagner@hms.harvard.edu.
Harvard University · USCenter for Integrated Protein Science Munich · DEUniversity of Zurich · CH

Funding

T CELL SPECIFIC TRANSCRIPTION COMPLEXESP01GM047467 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAGNER, GERHARD · 1992 to 2017
$28.6M
OverallP41EB002026 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GRIFFIN, ROBERT GUY · 2003 to 2018
$17.9M
Project 4 (Goethe University of Frankfurt)U54GM094608 · NIGMS · HARVARD MEDICAL SCHOOL · PI CHOU, JAMES JEIWEN · 2010 to 2014
$11.5M
NIBIB NIH HHS P41 EB002026NIGMS NIH HHS P01 GM047467NIGMS NIH HHS U54 GM094608
6 · The paper itself

Abstract

Heterotrimeric G proteins play a pivotal role in the signal-transduction pathways initiated by G-protein-coupled receptor (GPCR) activation. Agonist-receptor binding causes GDP-to-GTP exchange and dissociation of the Gα subunit from the heterotrimeric G protein, leading to downstream signaling. Here, we studied the internal mobility of a G-protein α subunit in its apo and nucleotide-bound forms and characterized their dynamical features at multiple time scales using solution NMR, small-angle X-ray scattering, and molecular dynamics simulations. We find that binding of GTP analogs leads to a rigid and closed arrangement of the Gα subdomain, whereas the apo and GDP-bound forms are considerably more open and dynamic. Furthermore, we were able to detect two conformational states of the Gα Ras domain in slow exchange whose populations are regulated by binding to nucleotides and a GPCR. One of these conformational states, the open state, binds to the GPCR; the second conformation, the closed state, shows no interaction with the receptor. Binding to the GPCR stabilizes the open state. This study provides an in-depth analysis of the conformational landscape and the switching function of a G-protein α subunit and the influence of a GPCR in that landscape.

Indexed as

Crystallography, X-RayGTP-Binding Protein alpha Subunits, Gi-GoGuanosine DiphosphateGuanosine TriphosphateHeterotrimeric GTP-Binding ProteinsHumansProtein BindingProtein ConformationReceptors, G-Protein-CoupledSignal TransductionGNAI1 protein, humanGTP-Binding Protein alpha Subunits, Gi-GoGuanosine DiphosphateGuanosine TriphosphateHeterotrimeric GTP-Binding ProteinsReceptors, G-Protein-CoupledGPCRNMRSAXSsignalingstructure

Identifiers

PMID27298341
PMCPMC4932968
OpenAlexW2424643883

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.