Scientists discover stable intermediate of serotonin receptor

Originally published by Max Delbrück Center for Molecular Medicine on September 4, 2024

Researchers have identified an intermediate form of the 5-HT3A serotonin receptor (blue). In its final form, a fifth subunit is added (green). The intermediate form presents a potential new drug target.. Credit: Max Delbrück Center

A new study published in The EMBO Journal points to new potential strategies to treat psychiatric and gastrointestinal disorders that are not well addressed by current medications. Dr. Bianca Introini and her colleagues in the In Situ Structural Biology lab of Professor Misha Kudryashev have identified a stable intermediate form of the pentameric serotonin-gated 5-HT3A receptor—a cellular membrane protein.

The researchers' ability to identify such a structure is exceptional, says Kudryashev, because intermediates of assembling membrane proteins are notoriously difficult to purify. The intermediate form could serve as a new drug target.

Serotonin is well known as a neurotransmitter that modulates neural activity and a variety of neuropsychological processes. Drugs that target serotonin receptors are used widely in psychiatry and neurology, for example. They are also given to patients to alleviate nausea and vomiting caused by chemotherapy and radiotherapy. However, these drugs often come with side effects that limit their use.

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