The Structural Arrangement and Dynamics of the Heteromeric GluK2/GluK5 Kainate Receptor As Determined by SmFRET

Overview

Journal Biochim Biophys Acta Biomembr

Publisher Elsevier

Specialties Biochemistry
Biophysics
Cell Biology

Date 2019 Jun 14

PMID 31194959

Citations 12

Authors

Douglas B Litwin

Nabina Paudyal

Elisa Carrillo

Vladimir Berka

Vasanthi Jayaraman

Affiliations

Soon will be listed here.

Abstract

Kainate receptors, which are glutamate activated excitatory neurotransmitter receptors, predominantly exist as heteromers of GluK2 and GluK5 subunits in the mammalian central nervous system. There are currently no structures of the full-length heteromeric kainate receptors. Here, we have used single molecule FRET to determine the specific arrangement of the GluK2 and GluK5 subunits within the dimer of dimers configuration in a full-length receptor. Additionally, we have also studied the dynamics and conformational heterogeneity of the amino-terminal and agonist-binding domain interfaces associated with the resting and desensitized states of the full-length heteromeric kainate receptor using FRET-based methods. The smFRET data are compared to similar experiments performed on the homomeric kainate receptor to provide insight into the differences in conformational dynamics that distinguish the two functionally. This article is part of a Special Issue entitled: Molecular biophysics of membranes and membrane proteins.

Citing Articles

Bi-directional allosteric pathway in NMDA receptor activation and modulation.

Bender P, Chakraborty S, Durham R, Berka V, Carrillo E, Jayaraman V Nat Commun. 2024; 15(1):8841.

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Single-Molecule FRET Analyses of NMDA Receptors.

Durham R, Jayaraman V Methods Mol Biol. 2024; 2799:225-242.

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Structural dynamics of GluK2 kainate receptors in apo and partial agonist bound states.

Bogdanovic N, Segura-Covarrubias G, Zhang L, Tajima N Res Sq. 2023; .

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Partial agonism in heteromeric GLUK2/GLUK5 kainate receptor.

Paudyal N, Das A, Carrillo E, Berka V, Jayaraman V Proteins. 2023; 93(1):134-144.

PMID: 37526035 PMC: 10830895. DOI: 10.1002/prot.26565.

Structure, Function, and Regulation of the Kainate Receptor.

Dhingra S, Yadav J, Kumar J Subcell Biochem. 2022; 99:317-350.

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References

Nayeem N, Mayans O, Green T . Correlating efficacy and desensitization with GluK2 ligand-binding domain movements. Open Biol. 2013; 3(5):130051. PMC: 3866869. DOI: 10.1098/rsob.130051. View

Bowie D . Ionotropic glutamate receptors & CNS disorders. CNS Neurol Disord Drug Targets. 2008; 7(2):129-43. PMC: 2662616. DOI: 10.2174/187152708784083821. View

Dingledine R, Borges K, Bowie D, Traynelis S . The glutamate receptor ion channels. Pharmacol Rev. 1999; 51(1):7-61. View

Reiner A, Arant R, Isacoff E . Assembly stoichiometry of the GluK2/GluK5 kainate receptor complex. Cell Rep. 2012; 1(3):234-40. PMC: 3324185. DOI: 10.1016/j.celrep.2012.01.003. View

Sun Y, Olson R, Horning M, Armstrong N, Mayer M, Gouaux E . Mechanism of glutamate receptor desensitization. Nature. 2002; 417(6886):245-53. DOI: 10.1038/417245a. View

Ramaswamy S, Cooper D, Poddar N, MacLean D, Rambhadran A, Taylor J . Role of conformational dynamics in α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor partial agonism. J Biol Chem. 2012; 287(52):43557-64. PMC: 3527942. DOI: 10.1074/jbc.M112.371815. View

Ren Z, Riley N, Garcia E, Sanders J, Swanson G, Marshall J . Multiple trafficking signals regulate kainate receptor KA2 subunit surface expression. J Neurosci. 2003; 23(16):6608-16. PMC: 6740640. View

MacLean D, Ramaswamy S, Du M, Howe J, Jayaraman V . Stargazin promotes closure of the AMPA receptor ligand-binding domain. J Gen Physiol. 2014; 144(6):503-12. PMC: 4242809. DOI: 10.1085/jgp.201411287. View

Dolino D, Rezaei Adariani S, Shaikh S, Jayaraman V, Sanabria H . Conformational Selection and Submillisecond Dynamics of the Ligand-binding Domain of the N-Methyl-d-aspartate Receptor. J Biol Chem. 2016; 291(31):16175-85. PMC: 4965566. DOI: 10.1074/jbc.M116.721274. View

10.

Kumar J, Schuck P, Mayer M . Structure and assembly mechanism for heteromeric kainate receptors. Neuron. 2011; 71(2):319-31. PMC: 3145919. DOI: 10.1016/j.neuron.2011.05.038. View

11.

Durr K, Chen L, Stein R, De Zorzi R, Folea I, Walz T . Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states. Cell. 2014; 158(4):778-792. PMC: 4263325. DOI: 10.1016/j.cell.2014.07.023. View

12.

Twomey E, Yelshanskaya M, Grassucci R, Frank J, Sobolevsky A . Channel opening and gating mechanism in AMPA-subtype glutamate receptors. Nature. 2017; 549(7670):60-65. PMC: 5743206. DOI: 10.1038/nature23479. View

13.

Gonzalez J, Du M, Parameshwaran K, Suppiramaniam V, Jayaraman V . Role of dimer interface in activation and desensitization in AMPA receptors. Proc Natl Acad Sci U S A. 2010; 107(21):9891-6. PMC: 2906876. DOI: 10.1073/pnas.0911854107. View

14.

Webb B, Sali A . Comparative Protein Structure Modeling Using MODELLER. Curr Protoc Bioinformatics. 2016; 54:5.6.1-5.6.37. PMC: 5031415. DOI: 10.1002/cpbi.3. View

15.

Shaikh S, Dolino D, Lee G, Chatterjee S, MacLean D, Flatebo C . Stargazin Modulation of AMPA Receptors. Cell Rep. 2016; 17(2):328-335. PMC: 5088782. DOI: 10.1016/j.celrep.2016.09.014. View

16.

Fisher M, Fisher J . Contributions of different kainate receptor subunits to the properties of recombinant homomeric and heteromeric receptors. Neuroscience. 2014; 278:70-80. PMC: 4172534. DOI: 10.1016/j.neuroscience.2014.08.009. View

17.

Meyerson J, Kumar J, Chittori S, Rao P, Pierson J, Bartesaghi A . Structural mechanism of glutamate receptor activation and desensitization. Nature. 2014; 514(7522):328-34. PMC: 4199900. DOI: 10.1038/nature13603. View

18.

Yelshanskaya M, Saotome K, Singh A, Sobolevsky A . Probing Intersubunit Interfaces in AMPA-subtype Ionotropic Glutamate Receptors. Sci Rep. 2016; 6:19082. PMC: 4703952. DOI: 10.1038/srep19082. View

19.

Dolino D, Chatterjee S, MacLean D, Flatebo C, Bishop L, Shaikh S . The structure-energy landscape of NMDA receptor gating. Nat Chem Biol. 2017; 13(12):1232-1238. PMC: 5698143. DOI: 10.1038/nchembio.2487. View

20.

Dawe G, Musgaard M, Andrews E, Daniels B, Aurousseau M, Biggin P . Defining the structural relationship between kainate-receptor deactivation and desensitization. Nat Struct Mol Biol. 2013; 20(9):1054-61. PMC: 4972573. DOI: 10.1038/nsmb.2654. View