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Related Concept Videos

Conformity01:20

Conformity

47.9K
Conformity is the change in a person’s behavior to go along with the group, even if that person does not agree with the group.
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¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

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At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
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¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR01:15

¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR

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The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
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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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Conformations of Butane02:20

Conformations of Butane

17.8K
Unlike ethane and propane that have only two major conformations, butane has more than two conformers. The staggered form of butane in which the bulky methyl groups on the two carbons are placed on opposite sides, that is, at a dihedral angle of 180°, is the lowest energy, most stable form — called the anti conformer. This conformation is stabilized due to the absence of steric repulsion between the largely spaced out methyl groups. The other two staggered conformations are...
17.8K
Conformations of Cycloalkanes02:29

Conformations of Cycloalkanes

14.2K
Adolf von Baeyer attempted to explain the instabilities of small and large cycloalkane rings using the concept of angle strain — the strain caused by the deviation of bond angles from the ideal 109.5° tetrahedral value for sp3  hybridized carbons. However, while cyclopropane and cyclobutane are strained, as expected from their highly compressed bond angles, cyclopentane is more strained than predicted, and cyclohexane is virtually strain-free. Hence, Baeyer’s theory that...
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Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
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Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

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Studying GPCR conformational dynamics by single molecule fluorescence.

Robert B Quast1, Emmanuel Margeat1

  • 1CBS, CNRS, INSERM, Université de Montpellier, Montpellier, France.

Molecular and Cellular Endocrinology
|June 5, 2019
PubMed
Summary

G protein-coupled receptors (GPCRs) exhibit significant structural flexibility, influencing their function and signaling. Single molecule fluorescence (SMF) methods, like smFRET, reveal real-time dynamics crucial for understanding GPCR activation and signaling specificity.

Keywords:
FRETFluorescenceGPCRSingle moleculeStructural dynamics

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) are critical membrane protein superfamilies involved in numerous physiological processes.
  • Recent findings suggest GPCRs possess inherent structural flexibility, moving beyond a simple inactive-to-active state model.
  • The functional and pharmacological implications of this dynamic flexibility are not yet fully understood.

Purpose of the Study:

  • To review the application of single molecule fluorescence (SMF) techniques in studying GPCR structural dynamics.
  • To highlight how SMF, particularly single molecule Förster resonance energy transfer (smFRET), provides insights into real-time conformational changes.
  • To discuss current understanding of GPCR activation and signaling, focusing on specific examples.

Main Methods:

  • Review of existing literature on GPCR structural dynamics.
  • Presentation of single molecule fluorescence (SMF) methodologies.
  • Detailed explanation of single molecule Förster resonance energy transfer (smFRET) for measuring distance changes and conformational dynamics.

Main Results:

  • GPCRs display significant structural flexibility, not limited to ligand-induced on/off states.
  • SMF techniques allow real-time monitoring of these dynamics in biologically relevant contexts.
  • smFRET is effective in capturing conformational changes at relevant biological timescales.

Conclusions:

  • GPCR structural flexibility plays a key role in fine-tuning receptor function and signal specificity.
  • SMF methods offer powerful tools to investigate these dynamics, advancing our understanding of GPCRs.
  • Insights from SMF studies, particularly on β2 adrenergic and metabotropic glutamate receptors, are reshaping views on GPCR activation and signaling.