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 via OpenAlex
Summary
AI-generated from the abstractSerotonin receptors are targets for drugs treating depression, obesity, and migraine headaches. Crystal structures of two serotonin receptor subtypes bound to antimigraine medications or a precursor of LSD reveal how subtle differences in ligand binding cause substantial differences in receptor signaling and biological responses. The structures show that the same ligand can activate one or both of the two main serotonin receptor signaling mechanisms, depending on which receptor it binds.
Study at a glance
| Characteristics | Structural biology study Peer reviewed |
|---|---|
| Topics | LSD Serotonin |
| Keywords | Functional selectivity G protein-coupled receptor Ergotamine Arrestin Signal transduction |
| Citations | 689 |
| Key finding | 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.