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G PROTEIN–COUPLED RECEPTORS

Asymmetry is central to excitatory glutamate receptor activation

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. 1.

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

    CAS  Article  Google Scholar 

  2. 2.

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

    CAS  Article  Google Scholar 

  3. 3.

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

    Article  PubMed  Google Scholar 

  4. 4.

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

    CAS  Article  Google Scholar 

  5. 5.

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

    CAS  Article  Google Scholar 

  6. 6.

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

    CAS  Article  Google Scholar 

  7. 7.

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

    CAS  Article  Google Scholar 

  8. 8.

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

    CAS  Article  Google Scholar 

  9. 9.

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

    CAS  Article  Google Scholar 

  10. 10.

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

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

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

    CAS  Article  Google Scholar 

  12. 12.

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

    CAS  Article  Google Scholar 

  13. 13.

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

    Article  Google Scholar 

  14. 14.

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

    CAS  Article  Google Scholar 

  15. 15.

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

    Article  Google Scholar 

  16. 16.

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

    CAS  Article  Google Scholar 

  17. 17.

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

    Article  Google Scholar 

  18. 18.

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

    CAS  Article  Google Scholar 

  19. 19.

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

    CAS  Article  Google Scholar 

  20. 20.

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

    CAS  Article  Google Scholar 

  21. 21.

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

    CAS  Article  Google Scholar 

  22. 22.

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

    CAS  Article  Google Scholar 

  23. 23.

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

    CAS  Article  Google Scholar 

  24. 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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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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