Journal article
Conformational dynamics in TRPV1 channels reported by an encoded coumarin amino acid
eLife, Vol.6, e28626
12/05/2017
DOI: 10.7554/eLife.28626
PMCID: PMC5716661
PMID: 29206105
Abstract
TRPV1 channels support the detection of noxious and nociceptive input. Currently available functional and structural data suggest that TRPV1 channels have two gates within their permeation pathway: one formed by a 'bundle-crossing' at the intracellular entrance and a second constriction at the selectivity filter. To describe conformational changes associated with channel gating, the fluorescent non-canonical amino acid coumarin-tyrosine was genetically encoded at Y671, a residue proximal to the selectivity filter. Total internal reflection fluorescence microscopy was performed to image the conformational dynamics of the channels in live cells. Photon counts and optical fluctuations from coumarin encoded within TRPV1 tetramers correlates with channel activation by capsaicin, providing an optical marker of conformational dynamics at the selectivity filter. In agreement with the fluorescence data, molecular dynamics simulations display alternating solvent exposure of Y671 in the closed and open states. Overall, the data point to a dynamic selectivity filter that may serve as a gate for permeation.
Details
- Title: Subtitle
- Conformational dynamics in TRPV1 channels reported by an encoded coumarin amino acid
- Creators
- Ximena Steinberg - Physiology Department, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileMarina A Kasimova - Institute for Computational Molecular Science, Temple University, Philadelphia, United StatesDeny Cabezas-Bratesco - Physiology Department, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileJason D Galpin - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, United StatesErnesto Ladron-de-Guevara - Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, MexicoFederica Villa - Dipartimento di Elettronica, Informazione e Bioingegneria (DEIB), Politecnico di Milano (POLIMI), Milano, ItalyVincenzo Carnevale - Institute for Computational Molecular Science, Temple University, Philadelphia, United StatesLeon Islas - Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, MexicoChristopher A Ahern - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, United StatesSebastian E Brauchi - Millennium Nucleus of Ion Channels-associated Diseases (MiNICAD), Iniciativa Cientifica Milenio, Santiago, Chile
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.6, e28626
- DOI
- 10.7554/eLife.28626
- PMID
- 29206105
- PMCID
- PMC5716661
- NLM abbreviation
- Elife
- eISSN
- 2050-084X
- Publisher
- England
- Grant note
- R01 GM122420 / NIGMS NIH HHS U54 GM087519 / NIGMS NIH HHS R01 GM093290 / NIGMS NIH HHS R01 GM106569 / NIGMS NIH HHS S10 OD020095 / NIH HHS
- Language
- English
- Date published
- 12/05/2017
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984071649102771
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