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Related Concept Videos

Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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GTPases and their Regulation02:14

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Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
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GTPases and their Regulation02:14

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G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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G Protein-coupled Receptors01:15

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Related Experiment Video

Updated: Nov 22, 2025

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
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Conformational switch that induces GDP release from Gi.

Donghee Ham1, Donghoon Ahn1, Janbolat Ashim2

  • 1School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea.

Journal of Structural Biology
|January 8, 2021
PubMed
Summary
This summary is machine-generated.

Dynamic changes in G protein phosphate-binding regions drive guanosine diphosphate (GDP) release. This study reveals key structural factors stabilizing the inactive GDP-bound state, clarifying GDP release mechanisms for guanine nucleotide-binding proteins.

Keywords:
GDP releaseHeterotrimeric guanine nucleotide-binding proteinsStructure

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Heterotrimeric guanine nucleotide-binding proteins (G proteins) regulate cellular signaling via conformational changes.
  • G protein alpha subunits (Gα) cycle between inactive guanosine diphosphate (GDP)-bound and active guanosine triphosphate (GTP)-bound states.
  • Guanine nucleotide-exchange factors (GEFs) like GPCRs, Ric8A, and GIV/Girdin catalyze nucleotide exchange, but GDP release mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the structural factors stabilizing the GDP-bound state of G proteins.
  • To identify the direct structural events triggering guanosine diphosphate (GDP) release from Gα subunits.

Main Methods:

  • Site-directed mutagenesis was employed to introduce point mutations in conserved residues of Gαi3.
  • GDP/GTP turnover rates were measured to assess nucleotide exchange dynamics.
  • Conformational changes and binding free energy between Gαi3 and GDP were analyzed.

Main Results:

  • Specific point mutations in Gαi3 significantly altered GDP/GTP turnover rates.
  • Dynamic alterations within the phosphate-binding regions were identified as critical for GDP release.
  • These conformational changes directly impact the stability of the GDP-bound state.

Conclusions:

  • Dynamic changes in the phosphate-binding region are the immediate cause of guanosine diphosphate (GDP) release.
  • Understanding these structural dynamics provides insights into G protein regulation and GEF interactions.
  • This research clarifies a fundamental step in G protein signaling pathways.