NMDA Receptor Opening and Closing-Transitions of a Molecular Machine Revealed by Molecular Dynamics

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00517459" target="_blank" >RIV/67985823:_____/19:00517459 - isvavai.cz</a>

Alternative codes found

RIV/86652036:_____/19:00517484 RIV/00216224:14310/19:00113388 RIV/00159816:_____/19:00072499

Result on the web

<a href="https://doi.org/10.3390/biom9100546" target="_blank" >https://doi.org/10.3390/biom9100546</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biom9100546" target="_blank" >10.3390/biom9100546</a>

Result language

angličtina

Original language name

NMDA Receptor Opening and Closing-Transitions of a Molecular Machine Revealed by Molecular Dynamics

Original language description

We report the first complete description of the molecular mechanisms behind the transition of the N-methyl-D-aspartate (NMDA) receptor from the state where the transmembrane domain (TMD) and the ion channel are in the open configuration to the relaxed unliganded state where the channel is closed. Using an aggregate of nearly 1 mu s of unbiased all-atom implicit membrane and solvent molecular dynamics (MD) simulations we identified distinct structural states of the NMDA receptor and revealed functionally important residues (GluN1/Glu522, GluN1/Arg695, and GluN2B/Asp786). The role of the “clamshell” motion of the ligand binding domain (LBD) lobes in the structural transition is supplemented by the observed structural similarity at the level of protein domains during the structural transition, combined with the overall large rearrangement necessary for the opening and closing of the receptor. The activated and open states of the receptor are structurally similar to the liganded crystal structure, while in the unliganded receptor the extracellular domains perform rearrangements leading to a clockwise rotation of up to 45 degrees around the longitudinal axis of the receptor, which closes the ion channel. The ligand-induced rotation of extracellular domains transferred by LBD-TMD linkers to the membrane-anchored ion channel is responsible for the opening and closing of the transmembrane ion channel, revealing the properties of NMDA receptor as a finely tuned molecular machine.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biomolecules

ISSN

2218-273X

e-ISSN

—

Volume of the periodical

9

Issue of the periodical within the volume

10

Country of publishing house

CH - SWITZERLAND

Number of pages

17

Pages from-to

546

UT code for WoS article

000497726800038

EID of the result in the Scopus database

2-s2.0-85072781240