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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Structural biology study Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | 5-HT Receptor Migraine Pharmacology Functional selectivity G protein-coupled receptor |
| Citations | 522 |
| Key points | 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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: Serotonin Supports
Crystal structures of two serotonin receptors reveal that ligand-binding differences alter receptor signaling, and the same ligand can activate one or both main signaling mechanisms depending on the receptor.
Synthesized
Citations in the library
Cited by 33
- Structural Features for Functional Selectivity at Serotonin Receptors Science March 21, 2013
- Crystal structure of an LSD-bound human serotonin receptor Cell January 26, 2017
- Structure-based discovery of nonhallucinogenic psychedelic analogs Science January 27, 2022
- LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1 Scientific Reports September 5, 2021
- Structural pharmacology and therapeutic potential of 5-methoxytryptamines. Nature June 1, 2024
and 28 more in the library