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G PROTEIN–COUPLED RECEPTORS

Asymmetry is central to excitatory glutamate receptor activation

Nature Structural & Molecular Biology volume 28, pages 633–635 (2021)Cite this article

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Dimeric multidomain metabotropic glutamate receptors modulate excitatory neurotransmission in the brain. Three articles in Nature provide unparalleled insights into how glutamate and drug-like molecules induce asymmetric shape changes in these multidomain receptors to promote coupling to an intracellular protein partner.

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Fig. 1: Full-length structures of dimeric mGlu receptors in different states: inactive, transitional and active–heterotrimeric Gi complexes.
Fig. 2: Intracellular views of homodimeric mGlu2 7TM domains reveal different dimerization interfaces.

References

  1. Lin, S. et al. Nature 594, 583–588 (2021).

    Article  CAS  Google Scholar 

  2. Du, J. et al. Nature 594, 589–593 (2021).

    Article  CAS  Google Scholar 

  3. Seven, A. B. et al. Nature https://doi.org/10.1038/s41586-021-03680-3 (2021).

    Article  PubMed  Google Scholar 

  4. Chappell, M. D. et al. J. Med. Chem. 59, 10974–10993 (2016).

    Article  CAS  Google Scholar 

  5. Muto, T., Tsuchiya, D., Morikawa, K. & Jingami, H. Proc. Natl Acad. Sci. USA 104, 3759–3764 (2007).

    Article  CAS  Google Scholar 

  6. Koehl, A. et al. Nature 566, 79–84 (2019).

    Article  CAS  Google Scholar 

  7. Kunishima, N. et al. Nature 407, 971–977 (2000).

    Article  CAS  Google Scholar 

  8. Tsuchiya, D., Kunishima, N., Kamiya, N., Jingami, H. & Morikawa, K. Proc. Natl Acad. Sci. USA 99, 2660–2665 (2002).

    Article  CAS  Google Scholar 

  9. Kniazeff, J. et al. Nat. Struct. Mol. Biol. 11, 706–713 (2004).

    Article  CAS  Google Scholar 

  10. Gao, Y. et al. Nature https://doi.org/10.1038/s41586-021-03691-0 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ling, S. et al. Cell Res. 31, 383–394 (2021).

    Article  CAS  Google Scholar 

  12. Xue, L. et al. Nat. Chem. Biol. 11, 134–140 (2015).

    Article  CAS  Google Scholar 

  13. Thibado, J. K. et al. Elife 10, e67027 (2021).

    Article  Google Scholar 

  14. Gutzeit, V. A. et al. Elife 8, e45116 (2019).

    Article  CAS  Google Scholar 

  15. O’Brien, D. E. et al. Mol. Pharmacol. 93, 526–540 (2018).

    Article  Google Scholar 

  16. Sengmany, K. et al. Neuropharmacology 149, 83–96 (2019).

    Article  CAS  Google Scholar 

  17. Liu, J. et al. Elife 6, e26985 (2017).

    Article  Google Scholar 

  18. Goudet, C. et al. J. Biol. Chem. 280, 24380–24385 (2005).

    Article  CAS  Google Scholar 

  19. Hlavackova, V. et al. EMBO J. 24, 499–509 (2005).

    Article  CAS  Google Scholar 

  20. Mao, C. et al. Cell Res. 30, 564–573 (2020).

    Article  CAS  Google Scholar 

  21. Shen, C. et al. Nature 594, 594–598 (2021).

    Article  CAS  Google Scholar 

  22. Wu, H. et al. Science 344, 58–64 (2014).

    Article  CAS  Google Scholar 

  23. Christopher, J. A. et al. J. Med. Chem. 58, 6653–6664 (2015).

    Article  CAS  Google Scholar 

  24. Doré, A. S. et al. Nature 511, 557–562 (2014).

    Article  Google Scholar 

Download references

Acknowledgements

K.J.G. is supported by an Australian Research Council Future Fellowship (FT170100392).

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Authors and Affiliations

  1. Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

    Karen J. Gregory

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  1. Karen J. Gregory
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Correspondence to Karen J. Gregory.

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Gregory, K.J. Asymmetry is central to excitatory glutamate receptor activation. Nat Struct Mol Biol 28, 633–635 (2021). https://doi.org/10.1038/s41594-021-00639-w

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