Structural Basis for Molecular Recognition at Serotonin Receptors
Chong Wang, Yi Jiang, Jinming Ma, Huixian Wu, Daniel Wacker, Vsevolod Katritch, Gye Won Han, Wei Liu, Xi‐ping Huang, Eyal Vardy, John D. Mccorvy, Xiang Gao, X. Edward Zhou, Karsten Melcher, Chenghai Zhang, Fang Bai, Huaiyu Yang, Linlin Yang, Hualiang Jiang, Bryan L. Roth, Vadim Cherezov, Raymond C. Stevens, H. Eric Xu
Science March 22, 2013 DOI: 10.1126/science.1232807 via OpenAlex
Summary
AI-generated from the abstractTwo research teams independently determined the crystal structures of two serotonin receptors bound to antimigraine drugs or a precursor of LSD. The structures show that subtle differences in how ligands bind to these receptors lead to substantial differences in the signals generated and the resulting biological responses. The same ligand can activate one or both of the two main serotonin receptor signaling mechanisms, depending on which specific receptor it binds to.
Study at a glance
| Characteristics | Structural biology study Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | 5-HT Receptor Migraine Pharmacology Functional selectivity |
| Citations | 522 |
| Key finding | Crystal structures of two serotonin receptors reveal that subtle differences in ligand binding cause substantial differences in receptor signaling and biological responses, and that the same ligand can activate one or both of the two main signaling mechanisms depending on the receptor. |
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.