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Related Concept Videos

GPCR Desensitization01:12

GPCR Desensitization

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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Cell-surface Signaling01:21

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Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
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Interaction of EM Radiation with Matter: Spectroscopy01:12

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Electromagnetic (EM) radiation can be considered an oscillating electric and magnetic field propagating through a medium that can interact with matter in its path. The electric field in the radiation can interact with electrical charges in the atoms or molecules in the matter. On the other hand, the magnetic field can interact with the magnetic field in the atomic nucleus. The study of the interaction between electromagnetic radiation and matter is termed spectroscopy. Spectroscopy is the study...
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Electromagnetic (EM) radiation consists of electric and magnetic field components oscillating in planes perpendicular to each other and mutually perpendicular to radiation propagation through space. EM radiation can be classified as a wave, characterized by the properties of waves such as wavelength (denoted as λ) and frequency (represented by ν).
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Cryo-electron Microscopy01:28

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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
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Endocrine Signaling01:45

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Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
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Illuminating GPCR Signaling by Cryo-EM.

Haaris Ahsan Safdari1, Shubhi Pandey2, Arun K Shukla2

  • 1Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.

Trends in Cell Biology
|June 28, 2018
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Summary

Cryo-electron microscopy (cryo-EM) advancements are revolutionizing G protein-coupled receptor (GPCR) studies. High-resolution structures of GPCR-G-protein complexes reveal crucial details for understanding cellular signaling pathways.

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Area of Science:

  • Structural biology
  • Biochemistry
  • Molecular cell biology

Background:

  • G protein-coupled receptors (GPCRs) are key transmembrane proteins mediating cellular responses.
  • Understanding GPCR structure is vital for drug discovery and deciphering signaling pathways.
  • Previous structural studies were limited by resolution and technique.

Purpose of the Study:

  • To leverage the cryo-electron microscopy (cryo-EM) resolution revolution for GPCR structural studies.
  • To determine high-resolution structures of GPCR-G-protein complexes.
  • To elucidate fine structural details of these complexes involved in cellular signaling.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) for high-resolution structure determination.
  • Advanced image processing and model building techniques.
  • Biochemical and biophysical characterization of GPCR-G-protein interactions.

Main Results:

  • Achieved unprecedented high-resolution structures of multiple GPCR-G-protein complexes.
  • Visualized intricate details of the interface between GPCRs and their cognate G proteins.
  • Provided atomic-level insights into the conformational states involved in signal transduction.

Conclusions:

  • The cryo-EM resolution revolution enables detailed structural analysis of GPCR-G-protein signaling.
  • These structures offer a foundation for understanding GPCR activation mechanisms.
  • Structural insights pave the way for targeted therapeutic interventions for GPCR-related diseases.