Images of 5-HT3 through Cryo-EM Aids in Cancer Therapy

Images of 5-HT3 through Cryo-EM Aids in Cancer Therapy

A team of international researchers took images of the receptor 5-HT3 in four different conformations, which will lead to the design of more efficient antinausea drugs for the treatment of patients undergoing therapy for cancers.

Cryo-EM helps to freeze biomolecules in action and visualize each of these at atomic resolution, which include key membrane proteins in several conformations. The researchers are able to develop snapshots that reveal the working of proteins and interactions of the molecules with one another. The team focused to find data from ESRF cryo-EM, which is the activation cycle of the 5-HT3 receptor, belonging to the family of serotonin receptors. Serotonin receptors are involved in influencing biological and neurological processes such as anxiety, appetite, mood, nausea, sleep, and thermoregulation, among others.

The researchers observed that 5-HT3 serotonin receptor cells changes its conformation during activation as it is a neurotransmitter-gated ion channel. Using cryo-electron microscopy, the team captured the image of receptor 5-HT3 in four different conformations. Out of these, three images were obtained at the Center for Cellular Imaging and Nano Analytics in Switzerland and the fourth at the European Synchrotron Radiation Facility. These images provided a full understanding of the activation mechanism of 5-HT3.

The findings were published in the journal Nature, on October 31, 2018, and involved the work of eminent researchers from Institute of Structural biology (IBS-mixed research unit CEA-CNRS-University Grenoble Alps), the Institut Pasteur, the University of Lorraine (France), the University of Copenhagen (Denmark), the University of Illinois (US), and the biotech company Theranyx.

Emily Sanders

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