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Title: Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [1];  [1];  [2];  [1]
  1. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Child Health and Human Development. Lab. of Cellular and Molecular Neurophysiology
  2. Univ. of Florida, St. Augustine, FL (United States). The Whitney Lab. for Marine Bioscience

Recent genome projects for ctenophores have revealed the presence of numerous ionotropic glutamate receptors (iGluRs) in Mnemiopsis leidyi and Pleurobrachia bachei, among our earliest metazoan ancestors. Sequence alignments and phylogenetic analysis show that these form a distinct clade from the well-characterized AMPA, kainate, and NMDA iGluR subtypes found in vertebrates. Although annotated as glutamate and kainate receptors, crystal structures of the ML032222a and PbiGluR3 ligand-binding domains (LBDs) reveal endogenous glycine in the binding pocket, whereas ligand-binding assays show that glycine binds with nanomolar affinity; biochemical assays and structural analysis establish that glutamate is occluded from the binding cavity. Further analysis reveals ctenophore-specific features, such as an interdomain Arg-Glu salt bridge, present only in subunits that bind glycine, but also a conserved disulfide in loop 1 of the LBD that is found in all vertebrate NMDA but not AMPA or kainate receptors. In this paper, we hypothesize that ctenophore iGluRs are related to an early ancestor of NMDA receptors, suggesting a common evolutionary path for ctenophores and bilaterian species, and finally suggest that future work should consider both glycine and glutamate as candidate neurotransmitters in ctenophore species.

Research Organization:
National Institutes of Health (NIH), Bethesda, MD (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States); National Aeronautics and Space Administration (NASA)
Contributing Organization:
Univ. of Florida, St. Augustine, FL (United States)
Grant/Contract Number:
W-31-109-Eng-38; 00093371
OSTI ID:
1228098
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 44; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 37 works
Citation information provided by
Web of Science

References (65)

Glutamate receptor desensitization is mediated by changes in quaternary structure of the ligand binding domain journal March 2013
Structure and Mechanism of Kainate Receptor Modulation by Anions journal March 2007
Crystal structure and association behaviour of the GluR2 amino-terminal domain journal May 2009
Very fast empirical prediction and rationalization of protein pKa values journal October 2005
Overview of the CCP 4 suite and current developments journal March 2011
Structural mechanism of glutamate receptor activation and desensitization journal August 2014
Evolutionary Profiles Derived from the QR Factorization of Multiple Structural Alignments Gives an Economy of Information journal February 2005
Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface journal November 2012
RNA editing in brain controls a determinant of ion flow in glutamate-gated channels journal October 1991
The ctenophore genome and the evolutionary origins of neural systems journal May 2014
Anions Mediate Ligand Binding in Adineta vaga Glutamate Receptor Ion Channels journal March 2013
An Improved General Amino Acid Replacement Matrix journal April 2008
Functional characterization of a potassium-selective prokaryotic glutamate receptor journal December 1999
Competitive antagonists and partial agonists at the glycine modulatory site of the mouse N-methyl-D-aspartate receptor. journal November 1990
HA-966 antagonizes N-methyl-D-aspartate receptors through a selective interaction with the glycine modulatory site journal June 1989
SignalP 4.0: discriminating signal peptides from transmembrane regions journal September 2011
Energetics of glutamate receptor ligand binding domain dimer assembly are modulated by allosteric ions journal July 2009
SEDPHAT – A platform for global ITC analysis and global multi-method analysis of molecular interactions journal April 2015
Ancient Protostome Origin of Chemosensory Ionotropic Glutamate Receptors and the Evolution of Insect Taste and Olfaction journal August 2010
X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor journal November 2009
Measuring substrate binding and affinity of purified membrane transport proteins using the scintillation proximity assay journal August 2012
Glutamate receptors at atomic resolution journal March 2006
Molecular Basis of Kainate Receptor Modulation by Sodium journal June 2008
Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the glutamate and serine complexes and a closed apo state journal August 2001
Mechanisms of activation, inhibition and specificity: crystal structures of the NMDA receptor NR1 ligand-binding core journal June 2003
Convergence of ion channel genome content in early animal evolution journal February 2015
Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors journal July 2008
Concanavalin A blocks desensitisation of glutamate receptors on insect muscle fibres journal February 1976
Characterization of a Soluble Ligand Binding Domain of the NMDA Receptor Regulatory Subunit NR3A journal April 2006
Crystal structure of a heterotetrameric NMDA receptor ion channel journal May 2014
Amino acid substitutions in the pore of rat glutamate receptors at sites influencing block by polyamines journal October 1999
Glycine potentiates the NMDA response in cultured mouse brain neurons journal February 1987
Cloned Glutamate Receptors journal March 1994
Multiple effects of spermine on N-methyl-D-aspartic acid receptor responses of rat cultured hippocampal neurones. journal May 1993
NMDA receptor structures reveal subunit arrangement and pore architecture journal June 2014
Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones journal May 1984
Conformational restriction blocks glutamate receptor desensitization journal November 2006
The Trichoplax genome and the nature of placozoans journal August 2008
Excitatory Amino Acid Transmitters journal April 1981
The N-terminal domain of GluR6-subtype glutamate receptor ion channels journal May 2009
Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins journal December 1994
Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A journal December 1993
Structural Similarities between Glutamate Receptor Channels and K+ Channels Examined by Scanning Mutagenesis journal March 2001
Features and development of Coot journal March 2010
A modern ionotropic glutamate receptor with a K+ selectivity signature sequence journal March 2011
Novel Cell Types, Neurosecretory Cells, and Body Plan of the Early-Diverging Metazoan Trichoplax adhaerens journal July 2014
Subunit arrangement and function in NMDA receptors journal November 2005
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Crystal Structures of the GluR5 and GluR6 Ligand Binding Cores: Molecular Mechanisms Underlying Kainate Receptor Selectivity journal February 2005
The Genome of the Ctenophore Mnemiopsis leidyi and Its Implications for Cell Type Evolution journal December 2013
Magnesium gates glutamate-activated channels in mouse central neurones journal February 1984
Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes journal August 1988
Crystal Structure of the GluR0 Ligand-Binding Core from Nostoc punctiforme in Complex with l-Glutamate: Structural Dissection of the Ligand Interaction and Subunit Interface journal February 2008
Functional reconstitution of Drosophila melanogaster NMJ glutamate receptors journal April 2015
NMRPipe: A multidimensional spectral processing system based on UNIX pipes journal November 1995
Detection of L -lactate in polyethylene glycol solutions confirms the identity of the active-site ligand in a proline dehydrogenase structure journal April 2004
Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block journal August 1995
MUSTANG: A multiple structural alignment algorithm journal May 2006
Modulation of the Dimer Interface at Ionotropic Glutamate-Like Receptor  2 by D-Serine and Extracellular Calcium journal January 2009
A kinetic analysis of the modulation of N-methyl-D-aspartic acid receptors by glycine in mouse cultured hippocampal neurones. journal September 1990
Structure and Dynamics of AMPA Receptor GluA2 in Resting, Pre-Open, and Desensitized States journal August 2014
VMD: Visual molecular dynamics journal February 1996
Phaser crystallographic software journal July 2007
The composition of Standard Seawater and the definition of the Reference-Composition Salinity Scale journal January 2008
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997

Cited By (13)

Neto-α Controls Synapse Organization and Homeostasis at the Drosophila Neuromuscular Junction journal July 2020
Family matters journal August 2013
Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events journal November 2018
Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels journal June 2016
Family Matters journal January 2018
The genome of the contractile demosponge Tethya wilhelma and the evolution of metazoan neural signalling pathways posted_content April 2017
Chemosensory adaptations of the mountain fly Drosophila nigrosparsa (Insecta: Diptera) through genomics’ and structural biology’s lenses journal March 2017
‘Family matters’: Ageing and the intergenerational social contract in urban Ahmedabad, Gujarat journal September 2017
The structural bases for agonist diversity in an Arabidopsis thaliana glutamate receptor-like channel journal December 2019
Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction posted_content October 2019
Family Matters: Family Quality of Life in Dementia journal June 2011
Family matters journal December 2018
Neuropeptidergic integration of behavior in Trichoplax adhaerens, an animal without synapses journal September 2017

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