Molecular dynamics simulations of the conformational. changes of the glutamate receptor ligand-binding core in the presence of glutamate and kainate

Citation
J. Mendieta et al., Molecular dynamics simulations of the conformational. changes of the glutamate receptor ligand-binding core in the presence of glutamate and kainate, PROTEINS, 44(4), 2001, pp. 460-469
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
44
Issue
4
Year of publication
2001
Pages
460 - 469
Database
ISI
SICI code
0887-3585(20010901)44:4<460:MDSOTC>2.0.ZU;2-#
Abstract
Excitatory synaptic transmission is mediated by ionotropic glutamate recept ors (iGluRs) through the induced transient opening of transmembrane ion cha nnels. The three-dimensional structure of the extracellular ligand-binding core of iGluRs shares the overall features of bacterial periplasmic binding proteins (PBPs). In both families of proteins, the ligand-binding site is arranged in two domains separated by a cleft and connected by two peptide s tretches. PBPs undergo a typical hinge motion of the two domains associated with ligand binding that leads to a conformational change from an open to a closed form. The common architecture suggests a similar closing mechanism in the ligand-binding core of iGluRs induced by the binding of specific ag onists. Starting from the experimentally determined kainate-bound closed fo rm of the S1S2 GluR2 construct, we have studied by means of molecular dynam ics simulations the opening motion of the ligand-binding core in the presen ce and in the absence of both glutamate and kainate. Our results suggest th at the opening/closing interdomain hinge motions are coupled to conformatio nal changes in the insertion region of the transmembrane segments. These ch anges are triggered by the interaction of the agonists with the essential G lu 209 residue. A plausible mechanism for the coupling of agonist binding t o channel gating is discussed. Proteins 2001;44:460-469. (C) 2001 Wiley-Lis s, Inc.