Allosteric binding site in a Cys-loop receptor ligand-binding domain unveiled in the crystal structure of ELIC in complex with chlorpromazine

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F16%3A00093868" target="_blank" >RIV/00216224:14740/16:00093868 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.pnas.org/content/113/43/E6696" target="_blank" >http://www.pnas.org/content/113/43/E6696</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.1603101113" target="_blank" >10.1073/pnas.1603101113</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Allosteric binding site in a Cys-loop receptor ligand-binding domain unveiled in the crystal structure of ELIC in complex with chlorpromazine

Popis výsledku v původním jazyce

Pentameric ligand-gated ion channels or Cys-loop receptors are responsible for fast inhibitory or excitatory synaptic transmission. The antipsychotic compound chlorpromazine is a widely used tool to probe the ion channel pore of the nicotinic acetylcholine receptor, which is a prototypical Cys-loop receptor. In this study, we determine the molecular determinants of chlorpromazine binding in the Erwinia ligand-gated ion channel (ELIC). We report the X-ray crystal structures of ELIC in complex with chlorpromazine or its brominated derivative bromopromazine. Unexpectedly, we do not find a chlorpromazine molecule in the channel pore of ELIC, but behind the beta 8-beta 9 loop in the extracellular ligand-binding domain. The beta 8-beta 9 loop is localized downstream from the neurotransmitter binding site and plays an important role in coupling of ligand binding to channel opening.

Název v anglickém jazyce

Allosteric binding site in a Cys-loop receptor ligand-binding domain unveiled in the crystal structure of ELIC in complex with chlorpromazine

Popis výsledku anglicky

Pentameric ligand-gated ion channels or Cys-loop receptors are responsible for fast inhibitory or excitatory synaptic transmission. The antipsychotic compound chlorpromazine is a widely used tool to probe the ion channel pore of the nicotinic acetylcholine receptor, which is a prototypical Cys-loop receptor. In this study, we determine the molecular determinants of chlorpromazine binding in the Erwinia ligand-gated ion channel (ELIC). We report the X-ray crystal structures of ELIC in complex with chlorpromazine or its brominated derivative bromopromazine. Unexpectedly, we do not find a chlorpromazine molecule in the channel pore of ELIC, but behind the beta 8-beta 9 loop in the extracellular ligand-binding domain. The beta 8-beta 9 loop is localized downstream from the neurotransmitter binding site and plays an important role in coupling of ligand binding to channel opening.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

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Svazek periodika

113

Číslo periodika v rámci svazku

43

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

"E6696"-"E6703"

Kód UT WoS článku

000386087100020

EID výsledku v databázi Scopus

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