Conformational spread and dynamics in allostery of NMDA receptors

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Texas Health Science Center at Houston

Details

Original languageEnglish (US)
Pages (from-to)3839-3847
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number7
StatusPublished - Feb 18 2020
Peer-reviewedYes

Abstract

Allostery can be manifested as a combination of repression and activation in multidomain proteins allowing for fine tuning of regulatory mechanisms. Here we have used single molecule fluorescence resonance energy transfer (smFRET) and molecular dynamics simulations to study the mechanism of allostery underlying negative cooperativity between the two agonists glutamate and glycine in the NMDA receptor. These data show that binding of one agonist leads to conformational flexibility and an increase in conformational spread at the second agonist site. Mutational and cross-linking studies show that the dimer–dimer interface at the agonist-binding domain mediates the allostery underlying the negative cooperativity. smFRET on the transmembrane segments shows that they are tightly coupled in the unliganded and single agonist-bound form and only upon binding both agonists the transmembrane domain explores looser packing which would facilitate activation.

    Research areas

  • Allostery, FRET, MD simulations, NMDA receptors

Citation formats

APA

Durham, R. J., Paudyal, N., Carrillo, E., Bhatia, N. K., Maclean, D. M., Berka, V., ... Jayaraman, V. (2020). Conformational spread and dynamics in allostery of NMDA receptors. Proceedings of the National Academy of Sciences of the United States of America, 117(7), 3839-3847. https://doi.org/10.1073/pnas.1910950117

Harvard

Durham, RJ, Paudyal, N, Carrillo, E, Bhatia, NK, Maclean, DM, Berka, V, Dolino, DM, Gorfe, AA & Jayaraman, V 2020, 'Conformational spread and dynamics in allostery of NMDA receptors', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 7, pp. 3839-3847. https://doi.org/10.1073/pnas.1910950117