Serotonin receptor structure revealed

August 5, 2014
3D structure of the serotonin receptor (blue ribbons) encased in a lipid membrane (black and red beads) © Hugues Nury - Institut de biologie structurale. Credit: CNRS/CEA/Université Joseph Fourier

The structure of a serotonin receptor has been completely deciphered for the first time using crystallography. This study, published online in Nature on August 3, 2014, opens the way towards the design of new drugs that might be able to control nausea, one of the main adverse effects of chemotherapy and anesthesia.

This work was carried out by a team at the Institut de Biologie Structurale (CNRS/CEA/Université Joseph Fourier) and the Physical Chemistry of Polymers and Membranes Laboratory (EPFL, Switzerland), working in collaboration with scientists from the Architecture et Fonction des Macromolécules Biologiques (CNRS/Université Aix-Marseille) and Dynamique Structurale des Macromolécules (CNRS/Institut Pasteur) laboratories, and with the company, Théranyx.

Communication between neurons in the brain is assured notably by receptors, i.e. cell membrane proteins, to which neurotransmitters can bind. Serotonin is one of the best known of these neurotransmitters. It is involved for example in the biology of the sleep-wake cycle, pain or anxiety. The under study forms part of the "Cys-loop" family of receptors, which are extremely important from a pharmacological point of view. This family notably includes the receptors to which nicotine binds, and also the target receptors for antidepressants (such as valium) or general anesthetic agents.

For the first time, scientists have determined the complete structure of a serotonin receptor in a mammal, the mouse, whose receptors are structurally similar to those of humans. Previously, it had only been possible to study in the Cys-loop family using homologs present in certain bacteria. In order to elucidate the complete structure of a serotoninergic receptor, the researchers had to overcome several obstacles, ranging from its production from cell lines cultivated in vitro to its purification and crystallization. They then imaged the protein by X-ray diffraction to reveal the position and organization of each of the amino acids making up its structure.

These findings shed new light on the functioning of this receptor, how it binds serotonin and transmits neural signals. They could pave the way for that may be able to control nausea, one of the principal of chemotherapy and anesthesia. Developing a compound directly based on the structure of the receptor may lead to the rapid discovery of a drug capable of binding to it and forming interactions. This receptor is also a potential target for other disorders that affect the digestive nervous system (such as ) or central nervous system (certain types of depression).

Explore further: The Journal of Biological Chemistry commemorates an important 1987 discovery

More information: "X-ray structure of the mouse serotonin 5-HT3 receptor." Ghérici Hassaine, Cédric Deluz, Luigino Grasso, Romain Wyss, Menno B. Tol, Ruud Hovius, Alexandra Graff, Henning Stahlberg, Takashi Tomizaki, Aline Desmyter, Christophe Moreau, Xiao-Dan Li, Frédéric Poitevin, Horst Vogel and Hugues Nury. Nature, online on August 3, 2014. DOI: 10.1038/nature13552

Related Stories

45 years on: How serotonin makes schistosome parasites move

January 16, 2014

Schistosoma mansoni and its close relatives are parasitic flatworms that affect millions worldwide and kill an estimated 250,000 people a year. A study published on January 16 in PLOS Pathogens identifies a new part of the ...

Switching off anxiety with light

April 7, 2014

Receptors for the messenger molecule serotonin can be modified in such a way that they can be activated by light. Together with colleagues, neuroscientists from the Ruhr-Universität Bochum (RUB) report on this finding in ...

Uncovering the 3-D structure of a key neuroreceptor

August 3, 2014

EPFL scientists reveal for the first time the 3D structure of a crucial neuroreceptor. The achievement has great implications for understanding the basic mechanism of electrical signal transmission between neurons and might ...

Recommended for you

Basic research fuels advanced discovery

August 26, 2016

Clinical trials and translational medicine have certainly given people hope and rapid pathways to cures for some of mankind's most troublesome diseases, but now is not the time to overlook the power of basic research, says ...

New avenue for understanding cause of common diseases

August 25, 2016

A ground-breaking Auckland study could lead to discoveries about many common diseases such as diabetes, cancer and dementia. The new finding could also illuminate the broader role of the enigmatic mitochondria in human development.

New method creates endless supply of kidney precursor cells

August 25, 2016

Salk Institute scientists have discovered the holy grail of endless youthfulness—at least when it comes to one type of human kidney precursor cell. Previous attempts to maintain cultures of the so-called nephron progenitor ...

Strict diet combats rare progeria aging disorders

August 25, 2016

Mice with a severe aging disease live three times longer if they eat thirty percent less. Moreover, they age much healthier than mice that eat as much as they want. These are findings of a joint study being published today ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.