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Related Concept Videos

Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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 affinity and are together...
GTPases and their Regulation02:14

GTPases and their Regulation

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, also known...
GTPases and their Regulation02:14

GTPases and their Regulation

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, also known...
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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.
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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.
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...

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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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G protein inactive and active forms investigated by simulation methods.

Kamil Khafizov1, Gianluca Lattanzi, Paolo Carloni

  • 1International School for Advanced Studies and INFM-DEMOCRITOS Modeling Center for Research in Atomistic Simulation, via Beirut 4, I-34014 Trieste, Italy.

Proteins
|December 18, 2008
PubMed
Summary
This summary is machine-generated.

Investigating G protein signaling, this study reveals key residues like Q204 in Galpha(i1) are crucial for interactions. Changes in G protein mobility and structure, particularly in the Switch IV region, are linked to its active and inactive states.

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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • G proteins are critical signal transducers, mediating cellular responses.
  • Understanding G protein conformational states is key to deciphering their function.
  • The Galpha(i1)beta(1)gamma(2) heterotrimer represents an important class of G proteins.

Purpose of the Study:

  • To investigate the structural and dynamic properties of G proteins in inactive, empty, and active states.
  • To identify key residues and regions involved in G protein interactions and conformational changes.
  • To elucidate the molecular mechanisms underlying G protein activation and regulation.

Main Methods:

  • Molecular dynamics simulations were employed to model G protein behavior.
  • Computational alanine scanning was used to assess the importance of specific residues.
  • Analysis focused on the Galpha(i1)beta(1)gamma(2) heterotrimer and the Galpha(i1) subunit.

Main Results:

  • Residue Q204 of Galpha(i1) is critical for binding Gbeta(1)gamma(2) and interacting with regulators of G protein signaling (RGS) proteins.
  • A mutation of Q204 to L, observed in diseases, maintains inactive state stability via van der Waals interactions.
  • The empty Galpha(i1) state exhibits active-like features, including a K46 rearrangement.
  • Switch IV region mobility increases from empty to active and further to inactive states.
  • Large-scale helical domain motion in the inactive state may facilitate GDP release.

Conclusions:

  • Specific residues and dynamic changes significantly influence G protein states and function.
  • The findings provide insights into G protein regulation and disease-associated mutations.
  • This study enhances the understanding of G protein signaling mechanisms at a molecular level.