Cargando…
Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG
Azobenzene-based photochromic lipids are valuable probes for the analysis of ion channel–lipid interactions. Rapid photoisomerization of these molecules enables the analysis of lipid gating kinetics and provides information on lipid sensing. Thermal relaxation of the metastable cis conformation to t...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221121/ https://www.ncbi.nlm.nih.gov/pubmed/35740924 http://dx.doi.org/10.3390/biom12060799 |
_version_ | 1784732543059230720 |
---|---|
author | Erkan-Candag, Hazel Krivic, Denis Gsell, Mathias A. F. Aleksanyan, Mina Stockner, Thomas Dimova, Rumiana Tiapko, Oleksandra Groschner, Klaus |
author_facet | Erkan-Candag, Hazel Krivic, Denis Gsell, Mathias A. F. Aleksanyan, Mina Stockner, Thomas Dimova, Rumiana Tiapko, Oleksandra Groschner, Klaus |
author_sort | Erkan-Candag, Hazel |
collection | PubMed |
description | Azobenzene-based photochromic lipids are valuable probes for the analysis of ion channel–lipid interactions. Rapid photoisomerization of these molecules enables the analysis of lipid gating kinetics and provides information on lipid sensing. Thermal relaxation of the metastable cis conformation to the trans conformation of azobenzene photolipids is rather slow in the dark and may be modified by ligand–protein interactions. Cis photolipid-induced changes in pure lipid membranes as visualized from the morphological response of giant unilamellar vesicles indicated that thermal cis–trans isomerization of both PhoDAG-1 and OptoDArG is essentially slow in the lipid bilayer environment. While the currents activated by cis PhoDAG remained stable upon termination of UV light exposure (dark, UV-OFF), cis OptoDArG-induced TRPC3/6/7 activity displayed a striking isoform-dependent exponential decay. The deactivation kinetics of cis OptoDArG-induced currents in the dark was sensitive to mutations in the L2 lipid coordination site of TRPC channels. We conclude that the binding of cis OptoDArG to TRPC channels promotes transition of cis OptoDArG to the trans conformation. This process is suggested to provide valuable information on DAG–ion channel interactions and may enable highly selective photopharmacological interventions. |
format | Online Article Text |
id | pubmed-9221121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92211212022-06-24 Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG Erkan-Candag, Hazel Krivic, Denis Gsell, Mathias A. F. Aleksanyan, Mina Stockner, Thomas Dimova, Rumiana Tiapko, Oleksandra Groschner, Klaus Biomolecules Article Azobenzene-based photochromic lipids are valuable probes for the analysis of ion channel–lipid interactions. Rapid photoisomerization of these molecules enables the analysis of lipid gating kinetics and provides information on lipid sensing. Thermal relaxation of the metastable cis conformation to the trans conformation of azobenzene photolipids is rather slow in the dark and may be modified by ligand–protein interactions. Cis photolipid-induced changes in pure lipid membranes as visualized from the morphological response of giant unilamellar vesicles indicated that thermal cis–trans isomerization of both PhoDAG-1 and OptoDArG is essentially slow in the lipid bilayer environment. While the currents activated by cis PhoDAG remained stable upon termination of UV light exposure (dark, UV-OFF), cis OptoDArG-induced TRPC3/6/7 activity displayed a striking isoform-dependent exponential decay. The deactivation kinetics of cis OptoDArG-induced currents in the dark was sensitive to mutations in the L2 lipid coordination site of TRPC channels. We conclude that the binding of cis OptoDArG to TRPC channels promotes transition of cis OptoDArG to the trans conformation. This process is suggested to provide valuable information on DAG–ion channel interactions and may enable highly selective photopharmacological interventions. MDPI 2022-06-07 /pmc/articles/PMC9221121/ /pubmed/35740924 http://dx.doi.org/10.3390/biom12060799 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Erkan-Candag, Hazel Krivic, Denis Gsell, Mathias A. F. Aleksanyan, Mina Stockner, Thomas Dimova, Rumiana Tiapko, Oleksandra Groschner, Klaus Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG |
title | Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG |
title_full | Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG |
title_fullStr | Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG |
title_full_unstemmed | Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG |
title_short | Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG |
title_sort | characterization of dag binding to trpc channels by target-dependent cis–trans isomerization of optodarg |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221121/ https://www.ncbi.nlm.nih.gov/pubmed/35740924 http://dx.doi.org/10.3390/biom12060799 |
work_keys_str_mv | AT erkancandaghazel characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg AT krivicdenis characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg AT gsellmathiasaf characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg AT aleksanyanmina characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg AT stocknerthomas characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg AT dimovarumiana characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg AT tiapkooleksandra characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg AT groschnerklaus characterizationofdagbindingtotrpcchannelsbytargetdependentcistransisomerizationofoptodarg |