PMID- 26153703
OWN - NLM
STAT- MEDLINE
DCOM- 20160329
LR  - 20230724
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Print)
IS  - 0006-3495 (Linking)
VI  - 109
IP  - 1
DP  - 2015 Jul 7
TI  - Conformational transitions in the glycine-bound GluN1 NMDA receptor LBD via 
      single-molecule FRET.
PG  - 66-75
LID - S0006-3495(15)00537-8 [pii]
LID - 10.1016/j.bpj.2015.05.025 [doi]
AB  - The N-methyl-D-aspartate receptor (NMDAR) is a member of the glutamate receptor 
      family of proteins and is responsible for excitatory transmission. Activation of 
      the receptor is thought to be controlled by conformational changes in the ligand 
      binding domain (LBD); however, glutamate receptor LBDs can occupy multiple 
      conformations even in the activated form. This work probes equilibrium 
      transitions among NMDAR LBD conformations by monitoring the distance across the 
      glycine-bound LBD cleft using single-molecule Forster resonance energy transfer 
      (smFRET). Recent improvements in photoprotection solutions allowed us to monitor 
      transitions among the multiple conformations. Also, we applied a recently 
      developed model-free algorithm called "step transition and state identification" 
      to identify the number of states, their smFRET efficiencies, and their interstate 
      kinetics. Reversible interstate conversions, corresponding to transitions among a 
      wide range of cleft widths, were identified in the glycine-bound LBD, on much 
      longer timescales compared to channel opening. These transitions were confirmed 
      to be equilibrium in nature by shifting the distribution reversibly via 
      denaturant. We found that the NMDAR LBD proceeds primarily from one adjacent 
      smFRET state to the next under equilibrium conditions, consistent with a 
      cleft-opening/closing mechanism. Overall, by analyzing the state-to-state 
      transition dynamics and distributions, we achieve insight into specifics of 
      long-lived LBD equilibrium structural dynamics, as well as obtain a more general 
      description of equilibrium folding/unfolding in a conformationally dynamic 
      protein. The relationship between such long-lived LBD dynamics and channel 
      function in the full receptor remains an open and interesting question.
CI  - Copyright (c) 2015 Biophysical Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Cooper, David R
AU  - Cooper DR
AD  - Department of Chemistry, Rice University, Houston, Texas.
FAU - Dolino, Drew M
AU  - Dolino DM
AD  - Center for Membrane Biology, Department of Biochemistry and Molecular Biology, 
      Graduate School of Biomedical Sciences, University of Texas Health Science 
      Center, Houston, Texas.
FAU - Jaurich, Henriette
AU  - Jaurich H
AD  - Department of Chemistry, Rice University, Houston, Texas.
FAU - Shuang, Bo
AU  - Shuang B
AD  - Department of Chemistry, Rice University, Houston, Texas.
FAU - Ramaswamy, Swarna
AU  - Ramaswamy S
AD  - Center for Membrane Biology, Department of Biochemistry and Molecular Biology, 
      Graduate School of Biomedical Sciences, University of Texas Health Science 
      Center, Houston, Texas.
FAU - Nurik, Caitlin E
AU  - Nurik CE
AD  - Center for Membrane Biology, Department of Biochemistry and Molecular Biology, 
      Graduate School of Biomedical Sciences, University of Texas Health Science 
      Center, Houston, Texas.
FAU - Chen, Jixin
AU  - Chen J
AD  - Department of Chemistry, Rice University, Houston, Texas.
FAU - Jayaraman, Vasanthi
AU  - Jayaraman V
AD  - Center for Membrane Biology, Department of Biochemistry and Molecular Biology, 
      Graduate School of Biomedical Sciences, University of Texas Health Science 
      Center, Houston, Texas. Electronic address: vasanthi.jayaraman@uth.tmc.edu.
FAU - Landes, Christy F
AU  - Landes CF
AD  - Department of Chemistry, Rice University, Houston, Texas; Department of 
      Electrical and Computer Engineering, Rice University, Houston, Texas. Electronic 
      address: cflandes@rice.edu.
LA  - eng
GR  - R01 AG017473/AG/NIA NIH HHS/United States
GR  - T32 GM008280/GM/NIGMS NIH HHS/United States
GR  - GM94246-01A1/GM/NIGMS NIH HHS/United States
GR  - R37 AG017473/AG/NIA NIH HHS/United States
GR  - R01 GM094246/GM/NIGMS NIH HHS/United States
GR  - 2T32 GM008280-26/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Algorithms
MH  - Anisotropy
MH  - Binding Sites
MH  - Escherichia coli
MH  - Fluorescence Resonance Energy Transfer/methods
MH  - Glycine/*metabolism
MH  - Kinetics
MH  - Models, Molecular
MH  - Mutation
MH  - Protein Conformation
MH  - Protein Denaturation
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
PMC - PMC4572502
EDAT- 2015/07/15 06:00
MHDA- 2016/03/30 06:00
PMCR- 2016/07/07
CRDT- 2015/07/09 06:00
PHST- 2014/08/08 00:00 [received]
PHST- 2015/05/15 00:00 [revised]
PHST- 2015/05/18 00:00 [accepted]
PHST- 2015/07/09 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/03/30 06:00 [medline]
PHST- 2016/07/07 00:00 [pmc-release]
AID - S0006-3495(15)00537-8 [pii]
AID - 10.1016/j.bpj.2015.05.025 [doi]
PST - ppublish
SO  - Biophys J. 2015 Jul 7;109(1):66-75. doi: 10.1016/j.bpj.2015.05.025.