Open AccessCharacteristic structural difference between inactive and active states of orexin 2 receptor determined using molecular dynamics simulations
Author(s) -
Shun Yokoi,
Ayori Mitsutake
Publication year - 2021
Publication title -
biophysical reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.766
H-Index - 39
eISSN - 1867-2469
pISSN - 1867-2450
DOI - 10.1007/s12551-021-00862-1
Subject(s) - transmembrane domain , transmembrane protein , molecular dynamics , helix (gastropod) , biophysics , receptor , chemistry , g protein coupled receptor , orexin , mutant , biochemistry , biology , computational chemistry , neuropeptide , ecology , snail , gene
To investigate the dynamics of the orexin 2 receptor, which is a class A G protein-coupled receptor, we recently performed several microsecond-scale molecular dynamics simulations of the wild-type protein, of a mutant that stabilizes the inactive state, and of constitutively active mutants of the class A G protein-coupled receptors. Herein, we review the results of these molecular dynamics simulations of the orexin 2 receptor. In these simulations, characteristic conformational changes were observed in the V309 6.40 Y mutant. The conformational changes were related to the outward movement of the transmembrane helix 6 and the inward movement of the transmembrane helix 7, which are common structural changes in the activation of G protein-coupled receptors. The index for the quantitative evaluation of the active and inactive states of class A G protein-coupled receptors and the mechanism of the inward movement of the transmembrane helix 7 were examined. In this review, we also discuss the activation mechanism by comparing the structures obtained from the molecular dynamics simulations with the structure of the active state of the orexin 2 receptor clarified by cryo-electron microscopy in the recent years.