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Related Concept Videos

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...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
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...
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...

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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions

Published on: July 18, 2013

GRIFFIN: a system for predicting GPCR-G-protein coupling selectivity using a support vector machine and a hidden

Yukimitsu Yabuki1, Takahiko Muramatsu, Takatsugu Hirokawa

  • 1Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan.

Nucleic Acids Research
|June 28, 2005
PubMed
Summary

GRIFFIN predicts G-protein coupled receptor (GPCR) and G-protein interactions using machine learning. This novel system achieves high accuracy in identifying specific G-protein binding partners for various GPCRs.

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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
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A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions

Published on: July 18, 2013

G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
09:12

G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay

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A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
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A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors

Published on: December 2, 2022

Area of Science:

  • Biochemistry and Molecular Biology
  • Computational Biology and Bioinformatics
  • Pharmacology

Background:

  • G-protein coupled receptors (GPCRs) are crucial transmembrane receptors involved in numerous cellular signaling pathways.
  • Understanding the specific coupling selectivity between GPCRs and G-proteins is essential for deciphering cellular responses and for drug discovery.
  • Current methods for predicting GPCR-G-protein interactions can be limited in scope and accuracy.

Purpose of the Study:

  • To develop and validate a novel computational system, GRIFFIN, for predicting G-protein coupling selectivity with high sensitivity and specificity.
  • To identify key structural features of ligands, GPCRs, and G-proteins that determine their interaction specificity.
  • To provide a reliable and accessible tool for researchers studying GPCR signaling.

Main Methods:

  • Development of the GRIFFIN (G-protein and Receptor Interaction Feature Finding INstrument) system, integrating a hierarchical Support Vector Machine (SVM) classifier and a Hidden Markov Model (HMM).
  • Selection of quantitative features from ligand, GPCR, and G-protein complex structures to serve as input vectors for the SVM.
  • Application of the SVM for Class A GPCRs and the HMM for opsins, olfactory subfamilies, and other minor GPCR classes (B, C, frizzled, smoothened).

Main Results:

  • GRIFFIN demonstrates high sensitivity and specificity in predicting GPCR-G-protein coupling selectivity, achieving over 85% accuracy on average for known GPCR sequences.
  • The hierarchical SVM effectively classifies coupling for the major Class A GPCR family.
  • The HMM component accurately predicts binding G-proteins for various subfamilies and minor GPCR classes.

Conclusions:

  • GRIFFIN provides a robust and accurate computational approach for predicting GPCR-G-protein coupling.
  • The system's ability to handle diverse GPCR classes enhances its utility in pharmacological research.
  • GRIFFIN is freely available, facilitating broader research into GPCR signaling mechanisms and drug development.