Structural insights into the activation of metabotropic glutamate receptors

Koehl, Antoine; Hu, Hongli; Feng, Dan; Sun, Bingfa; Zhang, Yan; Robertson, Michael J.; Chu, Matthew; Kobilka, Tong Sun; Laeremans, Toon; Steyaert, Jan; Tarrasch, Jeffrey; Dutta, Somnath; Fonseca, Rasmus; Weis, William I.; Mathiesen, Jesper M.; Skiniotis, Georgios; Kobilka, Brian K.

doi:10.1038/s41586-019-0881-4

Title: Structural insights into the activation of metabotropic glutamate receptors

Journal Article · Wed Jan 23 00:00:00 EST 2019 · Nature (London)

DOI:https://doi.org/10.1038/s41586-019-0881-4· OSTI ID:1497167

Koehl, Antoine; Hu, Hongli; Feng, Dan; Sun, Bingfa; Zhang, Yan; Robertson, Michael J.; Chu, Matthew; Kobilka, Tong Sun; Laeremans, Toon; Steyaert, Jan; Tarrasch, Jeffrey; Dutta, Somnath; Fonseca, Rasmus; Weis, William I.; Mathiesen, Jesper M.; Skiniotis, Georgios; Kobilka, Brian K.

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1497167

Journal Information:: Nature (London), Vol. 566, Issue 7742; ISSN 0028-0836

Publisher:: Nature Publishing Group

Country of Publication:: United States

Language:: ENGLISH

References (59)

Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease Niswender, Colleen M.; Conn, P. Jeffrey Annual Review of Pharmacology and Toxicology, Vol. 50, Issue 1 https://doi.org/10.1146/annurev.pharmtox.011008.145533	journal	February 2010
Organization and functions of mGlu and GABAB receptor complexes Pin, Jean-Philippe; Bettler, Bernhard Nature, Vol. 540, Issue 7631 https://doi.org/10.1038/nature20566	journal	December 2016
Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor Kunishima, Naoki; Shimada, Yoshimi; Tsuji, Yuji Nature, Vol. 407, Issue 6807 https://doi.org/10.1038/35039564	journal	October 2000
Closed state of both binding domains of homodimeric mGlu receptors is required for full activity Kniazeff, Julie; Bessis, Anne-Sophie; Maurel, Damien Nature Structural & Molecular Biology, Vol. 11, Issue 8 https://doi.org/10.1038/nsmb794	journal	July 2004
Sequential Inter- and Intrasubunit Rearrangements During Activation of Dimeric Metabotropic Glutamate Receptor 1 Hlavackova, V.; Zabel, U.; Frankova, D. Science Signaling, Vol. 5, Issue 237 https://doi.org/10.1126/scisignal.2002720	journal	August 2012
Structure of a Class C GPCR Metabotropic Glutamate Receptor 1 Bound to an Allosteric Modulator Wu, Huixian; Wang, Chong; Gregory, Karen J. Science, Vol. 344, Issue 6179 https://doi.org/10.1126/science.1249489	journal	March 2014
Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain Doré, Andrew S.; Okrasa, Krzysztof; Patel, Jayesh C. Nature, Vol. 511, Issue 7511 https://doi.org/10.1038/nature13396	journal	July 2014
Fragment and Structure-Based Drug Discovery for a Class C GPCR: Discovery of the mGlu ₅ Negative Allosteric Modulator HTL14242 (3-Chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile) Christopher, John A.; Aves, Sarah J.; Bennett, Kirstie A. Journal of Medicinal Chemistry, Vol. 58, Issue 16 https://doi.org/10.1021/acs.jmedchem.5b00892	journal	August 2015
Structure-Based Optimization Strategies for G Protein-Coupled Receptor (GPCR) Allosteric Modulators: A Case Study from Analyses of New Metabotropic Glutamate Receptor 5 (mGlu ₅ ) X-ray Structures Christopher, John A.; Orgován, Zoltán; Congreve, Miles Journal of Medicinal Chemistry, Vol. 62, Issue 1 https://doi.org/10.1021/acs.jmedchem.7b01722	journal	February 2018
Structural insights into G-protein-coupled receptor allostery Thal, David M.; Glukhova, Alisa; Sexton, Patrick M. Nature, Vol. 559, Issue 7712 https://doi.org/10.1038/s41586-018-0259-z	journal	July 2018
Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors Goudet, C.; Gaven, F.; Kniazeff, J. Proceedings of the National Academy of Sciences, Vol. 101, Issue 1 https://doi.org/10.1073/pnas.0304699101	journal	December 2003
Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling El Moustaine, D.; Granier, S.; Doumazane, E. Proceedings of the National Academy of Sciences, Vol. 109, Issue 40 https://doi.org/10.1073/pnas.1205838109	journal	September 2012
Nanobodies to Study G Protein–Coupled Receptor Structure and Function Manglik, Aashish; Kobilka, Brian K.; Steyaert, Jan Annual Review of Pharmacology and Toxicology, Vol. 57, Issue 1 https://doi.org/10.1146/annurev-pharmtox-010716-104710	journal	January 2017
A Novel Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Has in Vivo Activity and Antipsychotic-Like Effects in Rat Behavioral Models Kinney, Gene G.; O'Brien, Julie A.; Lemaire, Wei Journal of Pharmacology and Experimental Therapeutics, Vol. 313, Issue 1 https://doi.org/10.1124/jpet.104.079244	journal	December 2004
Investigating Metabotropic Glutamate Receptor 5 Allosteric Modulator Cooperativity, Affinity, and Agonism: Enriching Structure-Function Studies and Structure-Activity Relationships Gregory, Karen J.; Noetzel, Meredith J.; Rook, Jerri M. Molecular Pharmacology, Vol. 82, Issue 5 https://doi.org/10.1124/mol.112.080531	journal	August 2012
Quantitative Analysis Reveals Multiple Mechanisms of Allosteric Modulation of the mGlu5 Receptor in Rat Astroglia Bradley, Sophie J.; Langmead, Christopher J.; Watson, Jeannette M. Molecular Pharmacology, Vol. 79, Issue 5 https://doi.org/10.1124/mol.110.068882	journal	February 2011
Functional Impact of Allosteric Agonist Activity of Selective Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 in Regulating Central Nervous System Function Noetzel, Meredith J.; Rook, Jerri M.; Vinson, Paige N. Molecular Pharmacology, Vol. 81, Issue 2 https://doi.org/10.1124/mol.111.075184	journal	October 2011
Effects of Positive Allosteric Modulators on Single-Cell Oscillatory Ca ²⁺ Signaling Initiated by the Type 5 Metabotropic Glutamate Receptor Bradley, Sophie J.; Watson, Jeannette M.; Challiss, R. A. John Molecular Pharmacology, Vol. 76, Issue 6 https://doi.org/10.1124/mol.109.059170	journal	September 2009
Illuminating the activation mechanisms and allosteric properties of metabotropic glutamate receptors Doumazane, E.; Scholler, P.; Fabre, L. Proceedings of the National Academy of Sciences, Vol. 110, Issue 15 https://doi.org/10.1073/pnas.1215615110	journal	March 2013
Discovery of (1 S ,2 R ,3 S ,4 S ,5 R ,6 R )-2-Amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY3020371·HCl): A Potent, Metabotropic Glutamate 2/3 Receptor Antagonist with Antidepressant-Like Activity Chappell, Mark D.; Li, Renhua; Smith, Stephon C. Journal of Medicinal Chemistry, Vol. 59, Issue 24 https://doi.org/10.1021/acs.jmedchem.6b01119	journal	December 2016
Interdomain movements in metabotropic glutamate receptor activation Huang, S.; Cao, J.; Jiang, M. Proceedings of the National Academy of Sciences, Vol. 108, Issue 37 https://doi.org/10.1073/pnas.1107775108	journal	September 2011
Synthesis and Simple ¹⁸ F-Labeling of 3-Fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile as a High Affinity Radioligand for Imaging Monkey Brain Metabotropic Glutamate Subtype-5 Receptors with Positron Emission Tomography Siméon, Fabrice G.; Brown, Amira K.; Zoghbi, Sami S. Journal of Medicinal Chemistry, Vol. 50, Issue 14 https://doi.org/10.1021/jm0701268	journal	July 2007
Structures of the extracellular regions of the group II/III metabotropic glutamate receptors Muto, T.; Tsuchiya, D.; Morikawa, K. Proceedings of the National Academy of Sciences, Vol. 104, Issue 10 https://doi.org/10.1073/pnas.0611577104	journal	February 2007
Cys-140 Is Critical for Metabotropic Glutamate Receptor-1 Dimerization Ray, Kausik; Hauschild, Benjamin C. Journal of Biological Chemistry, Vol. 275, Issue 44 https://doi.org/10.1074/jbc.M005581200	journal	August 2000
Structural Insights into the Dynamic Process of β 2 -Adrenergic Receptor Signaling Manglik, Aashish; Kim, Tae Hun; Masureel, Matthieu Cell, Vol. 161, Issue 5 https://doi.org/10.1016/j.cell.2015.04.043	journal	May 2015
Structure and function of an irreversible agonist-β2 adrenoceptor complex Rosenbaum, Daniel M.; Zhang, Cheng; Lyons, Joseph A. Nature, Vol. 469, Issue 7329 https://doi.org/10.1038/nature09665	journal	January 2011
Mechanism of Assembly and Cooperativity of Homomeric and Heteromeric Metabotropic Glutamate Receptors Levitz, Joshua; Habrian, Chris; Bharill, Shashank Neuron, Vol. 92, Issue 1 https://doi.org/10.1016/j.neuron.2016.08.036	journal	October 2016
Identifying G protein-coupled receptor dimers from crystal packings Stenkamp, Ronald E. Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 7 https://doi.org/10.1107/S2059798318008136	journal	June 2018
G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function Milligan, Graeme British Journal of Pharmacology, Vol. 158, Issue 1 https://doi.org/10.1111/j.1476-5381.2009.00169.x	journal	September 2009
A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer James, John R.; Oliveira, Marta I.; Carmo, Alexandre M. Nature Methods, Vol. 3, Issue 12 https://doi.org/10.1038/nmeth978	journal	November 2006
Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer Xue, Li; Rovira, Xavier; Scholler, Pauline Nature Chemical Biology, Vol. 11, Issue 2 https://doi.org/10.1038/nchembio.1711	journal	December 2014
Generic GPCR residue numbers – aligning topology maps while minding the gaps Isberg, Vignir; de Graaf, Chris; Bortolato, Andrea Trends in Pharmacological Sciences, Vol. 36, Issue 1 https://doi.org/10.1016/j.tips.2014.11.001	journal	January 2015
Structural mechanism of ligand activation in human GABAB receptor Geng, Yong; Bush, Martin; Mosyak, Lidia Nature, Vol. 504, Issue 7479 https://doi.org/10.1038/nature12725	journal	December 2013
Structural mechanism of ligand activation in human calcium-sensing receptor Geng, Yong; Mosyak, Lidia; Kurinov, Igor eLife, Vol. 5 https://doi.org/10.7554/eLife.13662	journal	July 2016
Characterization of metabotropic glutamate receptors coupled to a pertussis toxin sensitive G-protein in bovine brain coated vesicles Martín, Mairena; Sanz, Juana M.; Cubero, Ana FEBS Letters, Vol. 316, Issue 2 https://doi.org/10.1016/0014-5793(93)81213-J	journal	January 1993
Molecular mechanism of positive allosteric modulation of the metabotropic glutamate receptor 2 by JNJ-46281222: Allosteric modulation of the mGlu Doornbos, Maarten L. J.; Pérez-Benito, Laura; Tresadern, Gary British Journal of Pharmacology, Vol. 173, Issue 3 https://doi.org/10.1111/bph.13390	journal	January 2016
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Scaling and assessment of data quality Evans, Philip Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82 https://doi.org/10.1107/S0907444905036693	journal	December 2005
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
SWISS-MODEL: homology modelling of protein structures and complexes Waterhouse, Andrew; Bertoni, Martino; Bienert, Stefan Nucleic Acids Research, Vol. 46, Issue W1 https://doi.org/10.1093/nar/gky427	journal	May 2018
The Phenix software for automated determination of macromolecular structures Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Methods, Vol. 55, Issue 1 https://doi.org/10.1016/j.ymeth.2011.07.005	journal	September 2011
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER Smart, Oliver S.; Womack, Thomas O.; Flensburg, Claus Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444911056058	journal	March 2012
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/S0907444996012255	journal	May 1997
MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG Williams, Christopher J.; Headd, Jeffrey J.; Moriarty, Nigel W. Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3330	journal	November 2017
A general protocol for the generation of Nanobodies for structural biology Pardon, Els; Laeremans, Toon; Triest, Sarah Nature Protocols, Vol. 9, Issue 3 https://doi.org/10.1038/nprot.2014.039	journal	February 2014
3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]- pyridine: A Potent and Highly Selective Metabotropic Glutamate Subtype 5 Receptor Antagonist with Anxiolytic Activity Cosford, Nicholas D. P.; Tehrani, Lida; Roppe, Jeffrey Journal of Medicinal Chemistry, Vol. 46, Issue 2 https://doi.org/10.1021/jm025570j	journal	January 2003
Discovery of Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 5 from a Series of N -(1,3-Diphenyl-1 H - pyrazol-5-yl)benzamides That Potentiate Receptor Function in Vivo Lindsley, Craig W.; Wisnoski, David D.; Leister, William H. Journal of Medicinal Chemistry, Vol. 47, Issue 24 https://doi.org/10.1021/jm049400d	journal	November 2004
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul Nature Methods, Vol. 14, Issue 4 https://doi.org/10.1038/nmeth.4193	journal	February 2017
Gctf: Real-time CTF determination and correction Zhang, Kai Journal of Structural Biology, Vol. 193, Issue 1 https://doi.org/10.1016/j.jsb.2015.11.003	journal	January 2016
RELION: Implementation of a Bayesian approach to cryo-EM structure determination Scheres, Sjors H. W. Journal of Structural Biology, Vol. 180, Issue 3, p. 519-530 https://doi.org/10.1016/j.jsb.2012.09.006	journal	December 2012
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination Punjani, Ali; Rubinstein, John L.; Fleet, David J. Nature Methods, Vol. 14, Issue 3 https://doi.org/10.1038/nmeth.4169	journal	February 2017
Bsoft: Image processing and molecular modeling for electron microscopy Heymann, J. Bernard; Belnap, David M. Journal of Structural Biology, Vol. 157, Issue 1 https://doi.org/10.1016/j.jsb.2006.06.006	journal	January 2007
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Scalable molecular dynamics with NAMD Phillips, James C.; Braun, Rosemary; Wang, Wei Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802 https://doi.org/10.1002/jcc.20289	journal	January 2005
Improved Peptide and Protein Torsional Energetics with the OPLS-AA Force Field Robertson, Michael J.; Tirado-Rives, Julian; Jorgensen, William L. Journal of Chemical Theory and Computation, Vol. 11, Issue 7 https://doi.org/10.1021/acs.jctc.5b00356	journal	June 2015
Insights on autophagosome–lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5 Nam, Sung-Eun; Cheung, Yiu Wing Sunny; Nguyen, Thanh Ngoc Communications Biology, Vol. 4, Issue 1 https://doi.org/10.1038/s42003-021-01830-x	journal	March 2021
Overview of the CCP4 suite and current developments. Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.52322	text	January 2011
Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling Manglik, Aashish; Kim, Tae Hun; Masureel, Matthieu Cell, Vol. 162, Issue 6 https://doi.org/10.1016/j.cell.2015.08.045	journal	September 2015

Cited By (9)

The role of water and protein flexibility in the structure-based virtual screening of allosteric GPCR modulators: an mGlu5 receptor case study Orgován, Zoltán; Ferenczy, György G.; Keserű, György M. Journal of Computer-Aided Molecular Design, Vol. 33, Issue 9 https://doi.org/10.1007/s10822-019-00224-w	journal	September 2019
Rearrangement of the transmembrane domain interfaces associated with the activation of a GPCR hetero-oligomer Xue, Li; Sun, Qian; Zhao, Han Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-10834-5	journal	June 2019
Conformational pathway provides unique sensitivity to a synaptic mGluR Habrian, Chris H.; Levitz, Joshua; Vyklicky, Vojtech Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13407-8	journal	December 2019
Stepwise activation of a class C GPCR begins with millisecond dimer rearrangement Grushevskyi, Eugene O.; Kukaj, Taulant; Schmauder, Ralf Proceedings of the National Academy of Sciences, Vol. 116, Issue 20 https://doi.org/10.1073/pnas.1900261116	journal	April 2019
Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits Park, Jihye; Selvam, Balaji; Sanematsu, Keisuke Journal of Biological Chemistry, Vol. 294, Issue 13 https://doi.org/10.1074/jbc.ra118.006173	journal	February 2019
Differential scanning fluorimetric analysis of the amino-acid binding to taste receptor using a model receptor protein, the ligand-binding domain of fish T1r2a/T1r3 Yoshida, Takashi; Yasui, Norihisa; Kusakabe, Yuko PLOS ONE, Vol. 14, Issue 10 https://doi.org/10.1371/journal.pone.0218909	journal	October 2019
Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors Llinas del Torrent, Claudia; Pérez-Benito, Laura; Tresadern, Gary Molecules, Vol. 24, Issue 6 https://doi.org/10.3390/molecules24061098	journal	March 2019
Conformational dynamics between transmembrane domains and allosteric modulation of a metabotropic glutamate receptor Gutzeit, Vanessa A.; Thibado, Jordana; Stor, Daniel Starer eLife, Vol. 8 https://doi.org/10.7554/elife.45116	journal	June 2019
DIMERBOW: exploring possible GPCR dimer interfaces García-Recio, Adrián; Navarro, Gemma; Franco, Rafael Bioinformatics, Vol. 36, Issue 10 https://doi.org/10.1093/bioinformatics/btaa117	journal	February 2020

Similar Records

Structural insights into the activation of metabotropic glutamate receptors

Journal Article · Wed Jan 23 00:00:00 EST 2019 · Nature (London) · OSTI ID:1497167

Koehl, Antoine; Hu, Hongli; Feng, Dan; +14 more

Author Correction: Structural insights into the activation of metabotropic glutamate receptors

Journal Article · Wed Feb 27 00:00:00 EST 2019 · Nature (London) · OSTI ID:1497167

Koehl, Antoine; Hu, Hongli; Feng, Dan; +14 more

Discovery of (1S,2R,3S,4S,5R,6R)-2-Amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY3020371·HCl): A Potent, Metabotropic Glutamate 2/3 Receptor Antagonist with Antidepressant-Like Activity

Journal Article · Fri Nov 11 00:00:00 EST 2016 · Journal of Medicinal Chemistry · OSTI ID:1497167

Chappell, Mark D.; Li, Renhua; Smith, Stephon C.; +43 more

Title: Structural insights into the activation of metabotropic glutamate receptors

Citation Formats

References (59)

Cited By (9)

Similar Records

Related Subjects