Structural basis for allosteric modulation of class b g protein-coupled receptors

Denise Wootten, Laurence J. Miller

Research output: Contribution to journalReview ArticleResearchpeer-review

22 Citations (Scopus)


Recent advances in our understanding of the structure and function of class B G protein-coupled receptors (GPCRs) provide multiple opportunities for targeted development of allosteric modulators. Given the pleiotropic signaling patterns emanating from these receptors in response to a variety of natural agonist ligands, modulators have the potential to sculpt the responses to meet distinct needs of different groups of patients. In this review, we provide insights into how this family of GPCRs differs from the rest of the superfamily, how orthosteric agonists bind and activate these receptors, the potential for allosteric modulators to interact with various regions of these targets, and the allosteric influence of endogenous proteins on the pharmacology of these receptors, all of which are important considerations when developing new therapies.

Original languageEnglish
Pages (from-to)89-107
Number of pages19
JournalAnnual Review of Pharmacology and Toxicology
Publication statusPublished - 6 Jan 2020


  • allosteric modulation
  • biased agonism
  • GPCRs
  • RAMPs
  • structure function

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