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Molecular lock regulates binding of glycine to a primitive NMDA receptor.

Yu A, Alberstein R, Thomas A, Zimmet A, Grey R, Mayer ML, Lau AY
Proc Natl Acad Sci U S A 113 E6786-E6795 (2016)
Cited: 23 times
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Abstract

The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine. X-ray crystallographic analysis details rearrangements in the binding pocket stemming from the mutations, and molecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulating ligand binding and that the free energy required to access open conformations in the glycine-bound LBD is largely responsible for differences in ligand affinity among the LBD variants.

Articles - 5cmc mentioned but not cited (4)

  1. Molecular lock regulates binding of glycine to a primitive NMDA receptor. Yu A, Alberstein R, Thomas A, Zimmet A, Grey R, Mayer ML, Lau AY. Proc Natl Acad Sci U S A 113 E6786-E6795 (2016)
  2. A saccharide-based binder for efficient polysulfide regulations in Li-S batteries. Huang Y, Shaibani M, Gamot TD, Wang M, Jovanović P, Dilusha Cooray MC, Mirshekarloo MS, Mulder RJ, Medhekar NV, Hill MR, Majumder M. Nat Commun 12 5375 (2021)
  3. Development of Active Packaging to Extend the Shelf Life of Agaricus bisporus by Using Plasma Technology. Chang CK, Cheng KC, Hou CY, Wu YS, Hsieh CW. Polymers (Basel) 13 2120 (2021)
  4. Nanoarchitectonics of Carbon Nanostructures: Sodium Dodecyl Sulfonate @ Sodium Chloride System. Chen Q, Li H. Nanomaterials (Basel) 12 1652 (2022)


Reviews citing this publication (6)

  1. Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters. Moroz LL, Romanova DY, Kohn AB. Philos Trans R Soc Lond B Biol Sci 376 20190762 (2021)
  2. Evolutionary origin of synapses and neurons - Bridging the gap. Burkhardt P, Sprecher SG. Bioessays 39 (2017)
  3. Evolution of glutamatergic signaling and synapses. Moroz LL, Nikitin MA, Poličar PG, Kohn AB, Romanova DY. Neuropharmacology 199 108740 (2021)
  4. Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia. de Bartolomeis A, Manchia M, Marmo F, Vellucci L, Iasevoli F, Barone A. Front Psychiatry 11 369 (2020)
  5. Activation and desensitization of ionotropic glutamate receptors by selectively triggering pre-existing motions. Krieger J, Lee JY, Greger IH, Bahar I. Neurosci Lett 700 22-29 (2019)
  6. Structural insights into NMDA receptor pharmacology. Zhou C, Tajima N. Biochem Soc Trans 51 1713-1731 (2023)

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  1. A multiscale coarse-grained model of the SARS-CoV-2 virion. Yu A, Pak AJ, He P, Monje-Galvan V, Casalino L, Gaieb Z, Dommer AC, Amaro RE, Voth GA. Biophys J 120 1097-1104 (2021)
  2. Atomic-scale characterization of mature HIV-1 capsid stabilization by inositol hexakisphosphate (IP6). Yu A, Lee EMY, Jin J, Voth GA. Sci Adv 6 eabc6465 (2020)
  3. Conformational spread and dynamics in allostery of NMDA receptors. Durham RJ, Paudyal N, Carrillo E, Bhatia NK, Maclean DM, Berka V, Dolino DM, Gorfe AA, Jayaraman V. Proc Natl Acad Sci U S A 117 3839-3847 (2020)
  4. Neurotransmitter Funneling Optimizes Glutamate Receptor Kinetics. Yu A, Salazar H, Plested AJR, Lau AY. Neuron 97 139-149.e4 (2018)
  5. Computer Simulations Predict High Structural Heterogeneity of Functional State of NMDA Receptors. Sinitskiy AV, Pande VS. Biophys J 115 841-852 (2018)
  6. D-Serine Potently Drives Ligand-Binding Domain Closure in the Ionotropic Glutamate Receptor GluD2. Chin AC, Yovanno RA, Wied TJ, Gershman A, Lau AY. Structure 28 1168-1178.e2 (2020)
  7. High Conformational Variability in the GluK2 Kainate Receptor Ligand-Binding Domain. Wied TJ, Chin AC, Lau AY. Structure 27 189-195.e2 (2019)
  8. Stability and molecular pathways to the formation of spin defects in silicon carbide. Lee EMY, Yu A, de Pablo JJ, Galli G. Nat Commun 12 6325 (2021)
  9. Family matters. Mayer ML, Jegla T. Elife 7 e43815 (2018)
  10. Ionotropic Receptors as a Driving Force behind Human Synapse Establishment. Viscardi LH, Imparato DO, Bortolini MC, Dalmolin RJS. Mol Biol Evol 38 735-744 (2021)
  11. The premetazoan ancestry of the synaptic toolkit and appearance of first neurons. Colgren J, Burkhardt P. Essays Biochem 66 781-795 (2022)
  12. Recording cilia activity in ctenophores: effects of nitric oxide and low molecular weight transmitters. Norekian TP, Moroz LL. Front Neurosci 17 1125476 (2023)
  13. Syncytial nets vs. chemical signaling: emerging properties of alternative integrative systems. Moroz LL. Front Cell Dev Biol 11 1320209 (2023)


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