Sandbox Reserved 1652: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Chloe Reynas (talk | contribs) No edit summary |
Chloe Reynas (talk | contribs) No edit summary |
||
| Line 36: | Line 36: | ||
The state of the channel is modulated by two types of molecules: agents that promote its opening of the channel, called [https://en.wikipedia.org/wiki/Agonist agonists], and agents that induce its closure or prevent its opening, called [https://en.wikipedia.org/wiki/Antagonist antagonists]. | The state of the channel is modulated by two types of molecules: agents that promote its opening of the channel, called [https://en.wikipedia.org/wiki/Agonist agonists], and agents that induce its closure or prevent its opening, called [https://en.wikipedia.org/wiki/Antagonist antagonists]. | ||
== Activators == | === Activators === | ||
#Capsaicin | |||
[[Image:128px-Capsaicin Formulae.png | thumb|Chemical structure of capsaicin]] | [[Image:128px-Capsaicin Formulae.png | thumb|Chemical structure of capsaicin]] | ||
| Line 51: | Line 51: | ||
This leads to the massive enter of Ca2+ and Na+ in the cytoplasm of the nerve fiber and to the depolarization of the nerve fiber. When depolarization reach a theshold value it triggers the generation of an [https://en.wikipedia.org/wiki/Action_potential action potential] causing a painful sensation.<ref>« TRPV1 », Wikipédia. sept. 09, 2020, Consulté le: déc. 28, 2020. [En ligne]. Disponible sur: https://fr.wikipedia.org/w/index.php?title=TRPV1&oldid=174570512</ref> | This leads to the massive enter of Ca2+ and Na+ in the cytoplasm of the nerve fiber and to the depolarization of the nerve fiber. When depolarization reach a theshold value it triggers the generation of an [https://en.wikipedia.org/wiki/Action_potential action potential] causing a painful sensation.<ref>« TRPV1 », Wikipédia. sept. 09, 2020, Consulté le: déc. 28, 2020. [En ligne]. Disponible sur: https://fr.wikipedia.org/w/index.php?title=TRPV1&oldid=174570512</ref> | ||
#Résinifératoxine (RTX) | |||
[[Image:Resiniferatoxin.png | thumb | Chemical structure of resiniferatoxine]] | [[Image:Resiniferatoxin.png | thumb | Chemical structure of resiniferatoxine]] | ||
| Line 66: | Line 66: | ||
The aromatic is located deeper in the sub-pocket near Y511 and is oriented almost parallel to the aromatic side chain of Y511, so it establishes a strong interaction π-π. The aromatic hydroxyl and methoxy groups of the RTX form strong hydrogen bonds with E570, R557 and S512. The ester group is linked to Y511 and T550 by hydrogen bonds.<ref>K. Elokely et al., « Understanding TRPV1 activation by ligands: Insights from the binding modes of capsaicin and resiniferatoxin », Proc. Natl. Acad. Sci., vol. 113, no 2, p. E137‑E145, janv. 2016, doi:10.1073/pnas.1517288113.</ref> | The aromatic is located deeper in the sub-pocket near Y511 and is oriented almost parallel to the aromatic side chain of Y511, so it establishes a strong interaction π-π. The aromatic hydroxyl and methoxy groups of the RTX form strong hydrogen bonds with E570, R557 and S512. The ester group is linked to Y511 and T550 by hydrogen bonds.<ref>K. Elokely et al., « Understanding TRPV1 activation by ligands: Insights from the binding modes of capsaicin and resiniferatoxin », Proc. Natl. Acad. Sci., vol. 113, no 2, p. E137‑E145, janv. 2016, doi:10.1073/pnas.1517288113.</ref> | ||
== Regulation == | === Regulation === | ||
#Sensitization | |||
'''Phosphorylation''' of the TRPV1 receptor leads to its sensitization. | '''Phosphorylation''' of the TRPV1 receptor leads to its sensitization. | ||
| Line 79: | Line 79: | ||
As a result phosphorylated TRPV1 are more responsive to agonist because they are overexpressed and the same quantity of agonist leads to a better openings of ion channels. | As a result phosphorylated TRPV1 are more responsive to agonist because they are overexpressed and the same quantity of agonist leads to a better openings of ion channels. | ||
#Desensitization | |||
A repeated exposure of TRPV1 to capsaicin fails to activate the receptor. It occurs by a CA2+-dependent mechanism that leads to a '''desphosphorylation''' by the calcineurin [https://en.wikipedia.org/wiki/Phosphatase phosphatase] of the serine and threonine residues which have been previously phosphorylated by PKA. Thus, the decrease in TRPV1 phosphorylation diminish the sensitivity of the capsaicin channel and so a decrease in the response of the capsaicin by '''negative feedback'''. | A repeated exposure of TRPV1 to capsaicin fails to activate the receptor. It occurs by a CA2+-dependent mechanism that leads to a '''desphosphorylation''' by the calcineurin [https://en.wikipedia.org/wiki/Phosphatase phosphatase] of the serine and threonine residues which have been previously phosphorylated by PKA. Thus, the decrease in TRPV1 phosphorylation diminish the sensitivity of the capsaicin channel and so a decrease in the response of the capsaicin by '''negative feedback'''. | ||
