The Conformational Equilibrium of the Neuropeptide Y2 Receptor in Bilayer Membranes

Structural transitions of crucial molecular switches of the activation of the human neuropeptide Y receptor type 2 are reported from the 13C‐tryptophan labeled molecule by solid‐state NMR spectroscopy in lipid membranes. The molecule shows high structural dynamics in the apo and agonist‐bound states, which is reduced by arrestin binding.

Abstract

Dynamic structural transitions within the seven‐transmembrane bundle represent the mechanism by which G‐protein‐coupled receptors convert an extracellular chemical signal into an intracellular biological function. Here, the conformational dynamics of the neuropeptide Y receptor type 2 (Y2R) during activation was investigated. The apo, full agonist‐, and arrestin‐bound states of Y2R were prepared by cell‐free expression, functional refolding, and reconstitution into lipid membranes. To study conformational transitions between these states, all six tryptophans of Y2R were 13C‐labeled. NMR‐signal assignment was achieved by dynamic‐nuclear‐polarization enhancement and the individual functional states of the receptor were characterized by monitoring 13C NMR chemical shifts. Activation of Y2R is mediated by molecular switches involving the toggle switch residue Trp2816.48 of the highly conserved SWLP motif and Trp3277.55 adjacent to the NPxxY motif. Furthermore, a conformationally preserved “cysteine lock”‐Trp11623.50 was identified.

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📅︎ Oct 01 2020
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The Conformational Equilibrium of the Neuropeptide Y2 Receptor in Bilayer Membranes

NMR spectroscopy sheds light on receptor activation: Molecular switches are conserved motifs of G protein‐coupled receptors that undergo structural changes during activation. Tryptophan residues are often part of these molecular switches and thus provide insights in the activation mechanism of the molecule. In their Research Article (DOI: 10.1002/anie.202006075) Daniel Huster et al. use NMR spectroscopy to monitor structural alterations of the neuropeptide Y1 receptor with atomic resolution observable by changes in the chemical shifts of six native tryptophan residues.

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📅︎ Nov 12 2020
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Ghrelin interacts with neuropeptide Y Y1 and opioid receptors to increase food reward. - PubMed ncbi.nlm.nih.gov/pubmed/2…
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NPY-Y1 receptor mediating anxiolytic-like effects of neuropeptide Y sciencedirect.com/science…
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👤︎ u/CL20
📅︎ Mar 14 2018
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Modulation of [3H]Dopamine Release from Rat Nucleus Accumbens by Neuropeptide Y May Involve a Sigma 1-like Receptor jpet.aspetjournals.org/co…
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📅︎ Nov 12 2018
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Peroxisome Proliferator-Activated Receptor γ Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus jneurosci.org/content/35/…
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📅︎ Apr 29 2015
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Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis stm.sciencemag.org/conten…
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👤︎ u/JanElizKor
📅︎ Aug 27 2021
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Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis stm.sciencemag.org/conten…
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👤︎ u/JanElizKor
📅︎ Aug 27 2021
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Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis stm.sciencemag.org/conten…
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👤︎ u/m3prx
📅︎ Aug 27 2021
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Neuropeptide oxytocin enhances μ opioid receptor signaling as a positive allosteric modulator doi.org/10.1016/j.jphs.20…
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📅︎ Dec 22 2019
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Neuropeptide oxytocin enhances μ opioid receptor signaling as a positive allosteric modulator sciencedirect.com/science…
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📅︎ Nov 11 2018
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Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation - Lijuan Xing1, Guangsen Shi, Yulia Mostovoy, Nicholas W. Gentry, Zenghua Fa1, Thomas B. McMahon, Pui-Yan Kwok, Christopher R. Jones, Louis J. Ptáček,† and Ying-Hui Fu. stm.sciencemag.org/conten…
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👤︎ u/swissseo
📅︎ Oct 19 2019
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"Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation", Xing et al 2019 gwern.net/docs/genetics/h…
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👤︎ u/gwern
📅︎ Oct 16 2019
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Do neurons contain receptors for other neurotransmitters / neuropeptides?

I would like to know if certain hormones, like dopamine, can bind to neurons in the brain and stimulate an action potential that leads to the release of neurotransmitters / neuropeptides.

Does anyone know?

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"Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation", Xing et al 2019 gwern.net/docs/genetics/h…
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👤︎ u/gwern
📅︎ Oct 16 2019
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Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor europeanneuropsychopharma…
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👤︎ u/CL20
📅︎ Jan 04 2018
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Neuropeptide S receptor gene — converging evidence for a role in panic disorder nature.com/articles/mp201…
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👤︎ u/CL20
📅︎ Apr 25 2018
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[Article]Neuropeptide Y1 and Y5 Receptor Antagonists as Potential Anti-Obesity Drugs: Current Status

Neuropeptide Y1 and Y5 Receptor Antagonists as Potential Anti-Obesity Drugs: Current Status

Antonio Moreno-Herrera, Abraham Garcia, Isidro Palos and Gildardo Tivera Mini-Reviews in Medicinal Chemistry, VOLUME: 14, ISSUE: 11, 2014, Pages 896-919 DOI: 10.2174/1389557514666141029233816

http://www.ingentaconnect.com/content/ben/mrmc/2014/00000014/00000011/art00003?crawler=true

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👤︎ u/hPI3K
📅︎ Feb 25 2015
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TIL some people truly are "born miserable." According to researchers, some people are genetically programmed to be more negative than others due to the levels of a molecule, neuropeptide Y, being lower in their brains than others. archive.indianexpress.com…
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👤︎ u/FrigoCoder
📅︎ Nov 02 2020
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If NMDA blockade can actually result in increased levels of glutamate, can antagonism of other substances (dopamine, serotonin, oxytocin, neuropeptide y etc,) do the same thing?
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📅︎ Mar 21 2021
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Are there gut bacteria that secrete Neuropeptide Y?
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📅︎ Jul 08 2021
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Running Y2 (Dual Y Axis) at different steps per mm to Y in marlin

Hopefully this is the right place to ask this. I'm designing a laser cutter using the parts from the 101hero since I assume most people would have upgraded from it by now and likely have the parts lying around with nothing to do with them. It will be 2 axis and there is 4 steppers total so I'm trying to run 2 steppers per axis, it uses 28byj-48 12v 1/32 steppers driven by A4988 stepper drivers however the 4th motor (the extruder) is 1/64. I was hoping to run 2 motors per axis to overcome the poor torque supplied by cheap steppers. Is there any way to run the second Y Axis motor at twice the speed (or the first at half). Or would using a 28 tooth pulley on one motor and a 14 tooth on the other the best option?

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👤︎ u/jclarke333
📅︎ Nov 18 2021
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The Conformational Equilibrium of the Neuropeptide Y2 Receptor in Bilayer Membranes

Dynamic structural transitions within the seven‐transmem­brane bundle represent the mechanism by which G protein‐coupled receptors convert an extracellular chemical signal into an intracel­lular biological function. Here, the conformational dynamics of the neuropeptide Y receptor type 2 (Y2R) during activation was investi­gated. The apo, full agonist‐ and arrestin‐bound states of Y2R were prepared by cell‐free expression, functional refolding, and reconsti­tution into lipid membranes. To study the conformational transitions between these states, all six tryptophans of Y2R were 13 C‐labeled. NMR signal assignment was achieved by dynamic nuclear polari­zation enhancement and the individual functional states of the recep­tor were characterized by monitoring 13 C NMR chemical shifts. Activation of Y2R is mediated by molecular switches involving the toggle switch residue Trp281 6.48 of the highly conserved SWLP motif and Trp327 7.55 adjacent to the NPxxY motif. Furthermore, a confor­mationally preserved “cysteine lock”‐Trp116 23.50 was identified.

https://ift.tt/3kFMgsG

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📅︎ Aug 13 2020
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