Optocontrol of glutamate receptor activity by single side-chain photoisomerization.

Abstract : Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation. PSAA photoisomerization at the GluN1 clamshell hinge is sufficient to control glycine sensitivity and activation efficacy. Strikingly, in the pore domain, flipping of a M3 residue within a conserved transmembrane cavity impacts both gating and permeation properties. Our study demonstrates the first detection of molecular rearrangements in real-time due to the reversible light-switching of single amino acid side-chains, adding a dynamic dimension to protein site-directed mutagenesis. This novel approach to interrogate neuronal protein function has general applicability in the fast expanding field of optopharmacology.
Type de document :
Article dans une revue
eLife, eLife Sciences Publication, 2017, 6, 〈10.7554/eLife.25808〉
Liste complète des métadonnées

Contributeur : Francesco Oteri <>
Soumis le : jeudi 14 septembre 2017 - 18:43:23
Dernière modification le : mercredi 27 septembre 2017 - 15:02:03

Lien texte intégral




Viktoria Klippenstein, Christian Hoppmann, Shixin Ye, Lei Wang, Pierre Paoletti. Optocontrol of glutamate receptor activity by single side-chain photoisomerization.. eLife, eLife Sciences Publication, 2017, 6, 〈10.7554/eLife.25808〉. 〈hal-01587934〉



Consultations de la notice