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Structural biology

A receptor that might block itself

Nature volume 544, pages 307–308 (2017)Cite this article

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The structure of the angiotensin II type 2 receptor reveals a potential mode of self-blocking action. This might explain its lack of signalling, and opens up avenues of investigation into its function and role in disease. See Article p.327

Throughout the human body, the coordination of cell activity by hormones and neurotransmitter molecules is mediated by a multitude of cell-membrane proteins known as G-protein-coupled receptors (GPCRs). These form the largest membrane-receptor family in humans, and are implicated in a range of disorders and diseases, including high blood pressure, migraine and cancer. It is essential for scientists to understand both the pharmacology and the structures of these receptors to develop new therapeutics. On page 327, Zhang et al.1 describe the crystal structure of a particularly enigmatic GPCR, the angiotensin II type 2 receptor (AT2R), which is a potential target for the treatment of cardiovascular disease2. Unexpectedly, its structure deviates from the conventional GPCR structure, a finding that might explain its unusual signalling behaviour.

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Figure 1: An active-like state of the angiotensin II type 2 receptor (AT2R).

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References

  1. Zhang, H. et al. Nature 544, 327–332 (2017).

    Article  ADS  CAS  Google Scholar 

  2. Dasgupta, C. & Zhang, L. Drug Discov. Today 16, 22–34 (2011).

    Article  CAS  Google Scholar 

  3. Venkatakrishnan, A. J. et al. Nature 494, 185–194 (2013).

    Article  ADS  CAS  Google Scholar 

  4. Horiuchi, M., Iwanami, J. & Mogi, M. Clin. Sci. 123, 193–203 (2012).

    Article  CAS  Google Scholar 

  5. White, J. F. et al. Nature 490, 508–513 (2012).

    Article  ADS  CAS  Google Scholar 

  6. Lebon, G. et al. Nature 474, 521–525 (2011).

    Article  CAS  Google Scholar 

  7. Xu, F. et al. Science 332, 322–327 (2011).

    Article  ADS  CAS  Google Scholar 

  8. Carpenter, B., Nehmé, R., Warne, T., Leslie, A. G. W. & Tate, C. G. Nature 536, 104–107 (2016).

    Article  ADS  CAS  Google Scholar 

  9. Lee, S., Bhattacharya, S., Tate, C. G., Grisshammer, R. & Vaidehi, N. J. Phys. Chem. B 119, 4917–4928 (2015).

    Article  CAS  Google Scholar 

  10. Smotrys, J. E. & Linder, M. E. Annu. Rev. Biochem. 73, 559–587 (2004).

    Article  CAS  Google Scholar 

  11. AbdAlla, S., Lother, H., Abdel-tawab, A. M. & Quitterer, U. J. Biol. Chem. 276, 39721–39726 (2001).

    Article  CAS  Google Scholar 

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  1. Christopher G. Tate is in the Department of Structural Studies, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.,

    Christopher G. Tate

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  1. Christopher G. Tate
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Correspondence to Christopher G. Tate.

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Competing interests

C.G.T. is a consultant and shareholder in Heptares Therapeutics.

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Tate, C. A receptor that might block itself. Nature 544, 307–308 (2017). https://doi.org/10.1038/nature21907

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