Structure-function studies of muscarinic acetylcholine receptors

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

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Other

14 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 - Handbook of Experimental Pharmacology 208
EditorsA D Fryer, A Christopoulos, N M Nathanson
Place of PublicationUSA
Pages29 - 48
Number of pages20
ISBN (Print)978-3-642-23273-2
Publication statusPublished - 2012

Cite this