Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR

Rika Numano, Stephanie Szobota, Albert Y. Lau, Pau Gorostiza, Matthew Volgraf, Benoit Roux, Dirk Trauner, Ehud Y. Isacoff

Research output: Contribution to journalArticle

Abstract

Photoswitched tethered ligands (PTLs) can be used to remotely control protein function with light. We have studied the geometric and conformational factors that determine the efficacy of PTL gating in the ionotropic glutamate receptor iGluR6 using a family of photoiosomerizable MAG (maleimide-azobenzene- glutamate) PTLs that covalently attach to the clamshell ligand-binding domain. Experiments and molecular dynamics simulations of the modified proteins show that optical switching depends on 2 factors: (i) the relative occupancy of the binding pocket in the 2 photoisomers of MAG and (ii) the degree of clamshell closure that is possible given the disposition of the MAG linker. A synthesized short version of MAG turns the channel on in either the cis or trans state, depending on the point of attachment. This yin/yang optical control makes it possible for 1 wavelength of light to elicit action potentials in one set of neurons, while deexciting a second set of neurons in the same preparation, whereas a second wavelength has the opposite effect. The ability to generate opposite responses with a single PTL and 2 versions of a target channel, which can be expressed in different cell types, paves the way for engineering opponency in neurons that mediate opposing functions.

Original languageEnglish (US)
Pages (from-to)6814-6819
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number16
DOIs
StatePublished - Apr 21 2009

Fingerprint

Glutamic Acid
Ligands
Neurons
Yin-Yang
Ionotropic Glutamate Receptors
Light
Molecular Dynamics Simulation
Action Potentials
Proteins
maleimide
azobenzene

Keywords

  • Glutamate receptor
  • Ion channel
  • Optics
  • Photoswitch

ASJC Scopus subject areas

  • General

Cite this

Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR. / Numano, Rika; Szobota, Stephanie; Lau, Albert Y.; Gorostiza, Pau; Volgraf, Matthew; Roux, Benoit; Trauner, Dirk; Isacoff, Ehud Y.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 16, 21.04.2009, p. 6814-6819.

Research output: Contribution to journalArticle

Numano, R, Szobota, S, Lau, AY, Gorostiza, P, Volgraf, M, Roux, B, Trauner, D & Isacoff, EY 2009, 'Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 16, pp. 6814-6819. https://doi.org/10.1073/pnas.0811899106
Numano, Rika ; Szobota, Stephanie ; Lau, Albert Y. ; Gorostiza, Pau ; Volgraf, Matthew ; Roux, Benoit ; Trauner, Dirk ; Isacoff, Ehud Y. / Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 16. pp. 6814-6819.
@article{3cc271de0ea247e5883c1336ab22d3f3,
title = "Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR",
abstract = "Photoswitched tethered ligands (PTLs) can be used to remotely control protein function with light. We have studied the geometric and conformational factors that determine the efficacy of PTL gating in the ionotropic glutamate receptor iGluR6 using a family of photoiosomerizable MAG (maleimide-azobenzene- glutamate) PTLs that covalently attach to the clamshell ligand-binding domain. Experiments and molecular dynamics simulations of the modified proteins show that optical switching depends on 2 factors: (i) the relative occupancy of the binding pocket in the 2 photoisomers of MAG and (ii) the degree of clamshell closure that is possible given the disposition of the MAG linker. A synthesized short version of MAG turns the channel on in either the cis or trans state, depending on the point of attachment. This yin/yang optical control makes it possible for 1 wavelength of light to elicit action potentials in one set of neurons, while deexciting a second set of neurons in the same preparation, whereas a second wavelength has the opposite effect. The ability to generate opposite responses with a single PTL and 2 versions of a target channel, which can be expressed in different cell types, paves the way for engineering opponency in neurons that mediate opposing functions.",
keywords = "Glutamate receptor, Ion channel, Optics, Photoswitch",
author = "Rika Numano and Stephanie Szobota and Lau, {Albert Y.} and Pau Gorostiza and Matthew Volgraf and Benoit Roux and Dirk Trauner and Isacoff, {Ehud Y.}",
year = "2009",
month = "4",
day = "21",
doi = "10.1073/pnas.0811899106",
language = "English (US)",
volume = "106",
pages = "6814--6819",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "16",

}

TY - JOUR

T1 - Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR

AU - Numano, Rika

AU - Szobota, Stephanie

AU - Lau, Albert Y.

AU - Gorostiza, Pau

AU - Volgraf, Matthew

AU - Roux, Benoit

AU - Trauner, Dirk

AU - Isacoff, Ehud Y.

PY - 2009/4/21

Y1 - 2009/4/21

N2 - Photoswitched tethered ligands (PTLs) can be used to remotely control protein function with light. We have studied the geometric and conformational factors that determine the efficacy of PTL gating in the ionotropic glutamate receptor iGluR6 using a family of photoiosomerizable MAG (maleimide-azobenzene- glutamate) PTLs that covalently attach to the clamshell ligand-binding domain. Experiments and molecular dynamics simulations of the modified proteins show that optical switching depends on 2 factors: (i) the relative occupancy of the binding pocket in the 2 photoisomers of MAG and (ii) the degree of clamshell closure that is possible given the disposition of the MAG linker. A synthesized short version of MAG turns the channel on in either the cis or trans state, depending on the point of attachment. This yin/yang optical control makes it possible for 1 wavelength of light to elicit action potentials in one set of neurons, while deexciting a second set of neurons in the same preparation, whereas a second wavelength has the opposite effect. The ability to generate opposite responses with a single PTL and 2 versions of a target channel, which can be expressed in different cell types, paves the way for engineering opponency in neurons that mediate opposing functions.

AB - Photoswitched tethered ligands (PTLs) can be used to remotely control protein function with light. We have studied the geometric and conformational factors that determine the efficacy of PTL gating in the ionotropic glutamate receptor iGluR6 using a family of photoiosomerizable MAG (maleimide-azobenzene- glutamate) PTLs that covalently attach to the clamshell ligand-binding domain. Experiments and molecular dynamics simulations of the modified proteins show that optical switching depends on 2 factors: (i) the relative occupancy of the binding pocket in the 2 photoisomers of MAG and (ii) the degree of clamshell closure that is possible given the disposition of the MAG linker. A synthesized short version of MAG turns the channel on in either the cis or trans state, depending on the point of attachment. This yin/yang optical control makes it possible for 1 wavelength of light to elicit action potentials in one set of neurons, while deexciting a second set of neurons in the same preparation, whereas a second wavelength has the opposite effect. The ability to generate opposite responses with a single PTL and 2 versions of a target channel, which can be expressed in different cell types, paves the way for engineering opponency in neurons that mediate opposing functions.

KW - Glutamate receptor

KW - Ion channel

KW - Optics

KW - Photoswitch

UR - http://www.scopus.com/inward/record.url?scp=66149153105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66149153105&partnerID=8YFLogxK

U2 - 10.1073/pnas.0811899106

DO - 10.1073/pnas.0811899106

M3 - Article

VL - 106

SP - 6814

EP - 6819

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

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

SN - 0027-8424

IS - 16

ER -