Scientists make a breakthrough in understanding serotonin receptors

Scientists make a breakthrough in understanding serotonin receptors

Les scientifiques font une percée dans la compréhension des récepteurs de la sérotonine

Graphic abstract. Credit: molecular cell (2022). DOI: 10.1016/j.molcel.2022.05.031

Serotonin (5-HT) is one of the main neurotransmitters of the human central nervous system and peripheral nervous system. It helps regulate appetite, memory, cognition and mood through serotonin (5-HTR) receptors.

A group of international scientists recently made a breakthrough in understanding the structure and function of serotonin receptors. This is the first time that researchers have reported the structures of 5-HT45-HT6and 5-HTseven receptors and resolved the structures of all 12 5-HT receptor subtypes.

The study was published online in molecular cell June 16.

Researchers led by H. Eric Xu from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences, in collaboration with researchers from Zhejiang University and the University of Copenhagen, have systematically revealed the structural basis recognition of serotonin receptor subtypes by small molecule ligands 5-HT and 5-CT. They also elucidated the molecular mechanism of the selective coupling of Gs and GI proteins by serotonin receptors.

The serotonin receptor family is one of the most complex subfamilies of the G protein-coupled receptor (GPCR) superfamily and contains 12 subtypes. Different receptor subtypes play different physiological roles in the human body and are coupled to different types of G proteins. Among them, 5-HT45-HT6and 5-HTseven receivers are mostly G-coupled downstreams protein and 5-HT1 and 5-HT5 receivers are mostly G-coupled downstreamI proteins.

Thanks to the structural comparison of these three Gs-G-coupled serotonin receptorsI/O-coupled serotonin receptors, and 19 additional G receptorss– and GI/Ocoupled to class A receptor structures, the team discovered a class-wide G-protein selectivity mechanism that uses the TM5 and TM6 switches.

“These findings advance the fundamental understanding of how serotonin receptors, the largest subfamily of class A GPCRs activated by the same endogenous ligand, create their wide diversity of cellular responses,” said Xu, author. study correspondent.

Moreover, this structural information on ligand recognition forms the basis for rational design of structure-based drugs targeting 5-HT.45-HT6and 5-HTseven receivers. This information also helps to clarify how to achieve ligand selectivity in the complex serotonergic system.

The achievement not only revealed the molecular mechanism of selective coupling of G proteins by class A GPCRs, but also filled the last gap in the structural analysis of 5-HT family receptors, according to the researchers.

These systematic studies of serotonin receptors have greatly enriched our understanding of the structure and function of the serotonin system. Since depression, schizophrenia and migraine may be linked to serotonin, this research may also contribute to treatments for these conditions.


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More information:
Sijie Huang et al, GPCRs drive Gi and Gs selectivity through TM5-TM6 switches as revealed by serotonin receptor structures, molecular cell (2022). DOI: 10.1016/j.molcel.2022.05.031

Provided by Chinese Academy of Sciences

Quote: Scientists Make Breakthrough in Understanding Serotonin Receptors (Jun 17, 2022) Retrieved June 18, 2022 from https://phys.org/news/2022-06-scientists-breakthrough-serotonin-receptors.html

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