Structure and function of serotonin G protein-coupled receptors. Pharmacol Ther 2015 Jun;150:129-42
Date
01/21/2015Pubmed ID
25601315Pubmed Central ID
PMC4414735DOI
10.1016/j.pharmthera.2015.01.009Scopus ID
2-s2.0-84939959325 (requires institutional sign-in at Scopus site) 305 CitationsAbstract
Serotonin receptors are prevalent throughout the nervous system and the periphery, and remain one of the most lucrative and promising drug discovery targets for disorders ranging from migraine headaches to neuropsychiatric disorders such as schizophrenia and depression. There are 14 distinct serotonin receptors, of which 13 are G protein-coupled receptors (GPCRs), which are targets for approximately 40% of the approved medicines. Recent crystallographic and biochemical evidence has provided a converging understanding of the basic structure and functional mechanics of GPCR activation. Currently, two GPCR crystal structures exist for the serotonin family, the 5-HT1B and 5-HT2B receptor, with the antimigraine and valvulopathic drug ergotamine bound. The first serotonin crystal structures not only provide the first evidence of serotonin receptor topography but also provide mechanistic explanations into functional selectivity or biased agonism. This review will detail the findings of these crystal structures from a molecular and mutagenesis perspective for driving rational drug design for novel therapeutics incorporating biased signaling.
Author List
McCorvy JD, Roth BLAuthor
John McCorvy PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Allosteric SiteAnimals
Ergotamine
GTP-Binding Proteins
Heart Valve Diseases
Humans
Migraine Disorders
Models, Molecular
Protein Conformation
Receptor, Serotonin, 5-HT1B
Receptor, Serotonin, 5-HT2B
Receptors, Serotonin
Serotonin Receptor Agonists
Signal Transduction
Vasoconstrictor Agents
