Structural Features for Functional Selectivity at Serotonin Receptors
Daniel Wacker, Chong Wang, Vsevolod Katritch, Gye Won Han, Xi-Ping Huang, Eyal Vardy, John D. Mccorvy, Yi Jiang, Meihua Chu, Fai Siu, Wei Liu, H. Eric Xu, Vadim Cherezov, Bryan L. Roth, Raymond C. Stevens
Science March 21, 2013 DOI: 10.1126/science.1232808 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Structural biology study Peer reviewed |
|---|---|
| Topics | LSD Serotonin |
| Keywords | Functional selectivity G protein-coupled receptor Ergotamine Arrestin Signal transduction 5-HT Receptor Cell biology |
| Citations | 689 |
| Key points | Crystal structures of two serotonin receptor subtypes reveal how ligand binding differences influence signaling mechanisms and biological responses. |
Abstract
Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of receptors bound to antimigraine medications or to a precursor of the hallucinogenic drug LSD. Subtle differences in the way particular ligands bind to the receptors cause substantial differences in the signals generated by the receptor and the consequent biological responses. The structures reveal how the same ligand can activate one or both of the two main serotonin receptor signaling mechanisms, depending on which particular receptor it binds.