TY - JOUR
T1 - Dynamics and allostery of the ionotropic glutamate receptors and the ligand binding domain
AU - Tobi, Dror
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - The dynamics of the ligand-binding domain (LBD) and the intact ionotropic glutamate receptor (iGluR) were studied using Gaussian Network Model (GNM) analysis. The dynamics of LBDs with various allosteric modulators is compared using a novel method of multiple alignment of GNM modes of motion. The analysis reveals that allosteric effectors change the dynamics of amino acids at the upper lobe interface of the LBD dimer as well as at the hinge region between the upper- and lower- lobes. For the intact glutamate receptor the analysis show that the clamshell-like movement of the LBD upper and lower lobes is coupled to the bending of the trans-membrane domain (TMD) helices which may open the channel pore. The results offer a new insight on the mechanism of action of allosteric modulators on the iGluR and support the notion of TMD helices bending as a possible mechanism for channel opening. In addition, the study validates the methodology of multiple GNM modes alignment as a useful tool to study allosteric effect and its relation to proteins dynamics.
AB - The dynamics of the ligand-binding domain (LBD) and the intact ionotropic glutamate receptor (iGluR) were studied using Gaussian Network Model (GNM) analysis. The dynamics of LBDs with various allosteric modulators is compared using a novel method of multiple alignment of GNM modes of motion. The analysis reveals that allosteric effectors change the dynamics of amino acids at the upper lobe interface of the LBD dimer as well as at the hinge region between the upper- and lower- lobes. For the intact glutamate receptor the analysis show that the clamshell-like movement of the LBD upper and lower lobes is coupled to the bending of the trans-membrane domain (TMD) helices which may open the channel pore. The results offer a new insight on the mechanism of action of allosteric modulators on the iGluR and support the notion of TMD helices bending as a possible mechanism for channel opening. In addition, the study validates the methodology of multiple GNM modes alignment as a useful tool to study allosteric effect and its relation to proteins dynamics.
KW - Allostery
KW - Gaussian network model
KW - Ionotropic glutamate receptors
KW - Multiple modes alignment
KW - Normal mode analysis
UR - http://www.scopus.com/inward/record.url?scp=84955215244&partnerID=8YFLogxK
U2 - 10.1002/prot.24977
DO - 10.1002/prot.24977
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C2 - 26677170
AN - SCOPUS:84955215244
SN - 0887-3585
VL - 84
SP - 267
EP - 277
JO - Proteins: Structure, Function and Bioinformatics
JF - Proteins: Structure, Function and Bioinformatics
IS - 2
ER -