In November 2017, a Titan Krios cryo-electron microscope (cryo-EM) was inaugurated at the ESRF, the European Synchrotron, France. Data collected on this cryo-EM features in a Nature publication describing the activation cycle of a serotonin receptor, which is targeted by medication against chemotherapy- and radiotherapy-induced nausea.
“This publication is a true reward for us: the first one in less than a year from inauguration and we hope this kind of rewards will grow in number”, explains Isai Kandiah, ESRF scientist who runs the facility. “It shows the revolution that cryo-EM is leading in structural biology”, she adds. Thanks to cryo-EM, researchers can now freeze biomolecules, including membrane proteins of high medical importance, in several different conformations in action and visualise each of these to atomic resolution. Cryo-EM thus allows researchers to produce snapshots revealing the dynamics of proteins when they interact with other molecules, information that is crucial both for a basic understanding of life’s chemistry and for the development of pharmaceuticals. The user programme of the cryo-electron microscope at the ESRF is run jointly with the European Molecular Biology Laboratory (EMBL), the Institut de Biologie Structurale (IBS) and the Institut Laue-Langevin (ILL).
The research in Nature is a result of an international collaboration of scientists from the Institute of Structural biology (IBS-mixed research unit CEA-CNRS-University Grenoble Alps), CEA, CNRS, the Institut Pasteur, the University of Lorraine (France), the University of Copenhagen (Denmark), the University of Illinois (US) and the biotech company Theranyx. The focus of the paper, featuring data from the ESRF cryo-EM, is the activation cycle of the 5-HT3 receptor, belonging to the family of serotonin receptors. These receptors are well-known because they influence various biological and neurological processes such as anxiety, appetite, mood, nausea, sleep and thermoregulation, among others. Unlike the other serotonin receptors, which are G protein-coupled receptors, 5-HT3 is a neurotransmitter-gated ion channel and changes its conformation during activation. It is present in the brain, as well as in the enteric nervous system, the peripheral nervous system that drives the digestive tract.
Image: A close-up view of the Cryo-EM at the ESRF.
Credit: S. Candé.