Conventional allosteric modulators of G protein–coupled receptors (GPCRs) bind their target from the extracellular site. A new study shows that a GPCR's intracellular face can likewise be exploited. In particular, they sensitize a class B GPCR for activation by a hardly active peptide-hormone metabolite.
References
Kenakin, T.P. Br. J. Pharmacol. 165, 1659–1669 (2012).
Nolte, W.M. et al. Nat. Chem. Biol. 10, 629–631 (2014).
Hollenstein, K. et al. Trends Pharmacol. Sci. 35, 12–22 (2014).
Koole, C. et al. Biochem. Soc. Trans. 41, 172–179 (2013).
Donnelly, D. Br. J. Pharmacol. 166, 27–41 (2012).
Sloop, K.W. et al. Diabetes 59, 3099–3107 (2010).
Bock, A. et al. Nat Commun. 3, 1044 (2012).
Kruse, A.C. et al. Nature 504, 101–106 (2013).
Dowal, L. et al. Proc. Natl. Acad. Sci. USA 108, 2951–2956 (2011).
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Mohr, K., Kostenis, E. A GPCR's back door. Nat Chem Biol 10, 609–610 (2014). https://doi.org/10.1038/nchembio.1583
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DOI: https://doi.org/10.1038/nchembio.1583
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