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Conformational dynamics in TRPV1 channels reported by an encoded coumarin amino acid
Steinberg, X Kasimova, MA Cabezas-Bratesco, D Galpin, JD Ladron-de-Guevara, E Villa, F Carnevale, V Islas, L Ahern, CA Brauchi, SE
Steinberg, X
Kasimova, MA
Cabezas-Bratesco, D
Galpin, JD
Ladron-de-Guevara, E
Villa, F
Carnevale, V
Islas, L
Ahern, CA
Brauchi, SE
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Genre
Journal Article
Date
2017-12-05
Advisor
Committee member
Group
Department
Subject
SPAD
TRPV1
biophysics
computational biology
coumarin
gating
non-canonical amino acids
none
pore
structural biology
systems biology
Capsaicin
Coumarins
HEK293 Cells
Humans
Intravital Microscopy
Microscopy, Fluorescence
Models, Molecular
Molecular Dynamics Simulation
Protein Conformation
Staining and Labeling
TRPV Cation Channels
Tyrosine
TRPV1
biophysics
computational biology
coumarin
gating
non-canonical amino acids
none
pore
structural biology
systems biology
Capsaicin
Coumarins
HEK293 Cells
Humans
Intravital Microscopy
Microscopy, Fluorescence
Models, Molecular
Molecular Dynamics Simulation
Protein Conformation
Staining and Labeling
TRPV Cation Channels
Tyrosine
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DOI
10.7554/eLife.28626
Abstract
© Steinberg et al. 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 0bundle-crossing0 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.
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eLife Sciences Publications, Ltd
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eLife
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