Structure-function studies of muscarinic acetylcholine receptors

Katie Leach, John Simms, Patrick M Sexton, Arthur Christopoulos

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

18 Citations (Scopus)


There has been great interest in the structure-function relationships of the muscarinic acetylcholine receptors (mAChRs) because these prototypical Family A/class 1 G protein-coupled receptors (GPCRs) are attractive therapeutic targets for both peripheral and central nervous system disorders. A multitude of drugs that act at the mAChRs have been identified over the years, but many of these show minimal selectivity for any one of the five mAChR subtypes over the others, which has hampered their development into therapeutics due to adverse side effects. The lack of drug specificity is primarily due to high sequence similarity in this family of receptor, especially in the orthosteric binding pocket. Thus, there remains an ongoing need for a molecular understanding of how mAChRs bind their ligands, and how selectivity in binding and activation can be achieved. Unfortunately, there remains a paucity of solved high-resolution structures of GPCRs, including the mAChRs, and thus most of our knowledge of structure-function mechanisms related to this receptor family to date has been obtained indirectly through approaches such as mutagenesis. Nonetheless, such studies have revealed a wealth of information that has led to novel insights and may be used to guide future rational drug design campaigns.

Original languageEnglish
Title of host publicationMuscarinic Receptors
EditorsAllison D. Fryer, Neil M. Nathanson, Arthur Christopoulos
PublisherSpringer Verlag
Number of pages20
ISBN (Electronic)9783642232749
ISBN (Print)9783642237232
Publication statusPublished - 2012

Publication series

NameHandbook of Experimental Pharmacoloy


  • Acetylcholine
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation
  • Receptors, Muscarinic
  • Signal Transduction
  • Structure-Activity Relationship
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review


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