For the first time, USC scientists have mapped out a neuroreceptor. This scientific breakthrough promises to revolutionize the engineering of drugs used to treat ailments such as Alzheimer's disease and schizophrenia.
The team produced the world's first high-resolution images of the á7 (Alpha 7) receptor, a molecule responsible for transmitting signals between neurons – particularly in regions of the brain believed to be associated with learning and memory.
Using the image, scientists will be better equipped to design pharmaceuticals specifically to interact with the receptor, instead of blindly using a trial-and-error approach.
"A lot of interest in this work will come from pharmaceutical companies," said corresponding author Lin Chen, professor of biological sciences and chemistry at the USC Dornsife College of Letters, Arts and Sciences. "They really have no clear picture of this. They don't know how or why [their drugs] work."
The high-resolution image will also help neuroscience researchers study how these receptors receive and transmit neuronal signals, a question that has puzzled researchers for decades.
The article, co-authored with scientists from the Keck School of Medicine of USC and the Mayo Clinic College of Medicine, appears in Nature Neuroscience this month.
The findings follow up on Chen's earlier landmark achievement, deciphering the inner workings of a nicotine receptor in 2007.
Developing an image of the á7 receptor was no simple task, which is partly why it has taken until now to achieve this despite the wide interest in the understanding the receptor's structure. Attempts to decipher neuroreceptors have been ongoing for 30 years.
"This has been a longstanding challenge," Chen said. The challenge is twofold, he said. It is difficult to obtain enough receptor protein for structural analysis, and the flexible nature of these receptors makes them difficult to crystallize — a necessary step for high-resolution imaging.
The biologist's usual go-to method to study such molecules — growing a large quantity using molecular cloning — failed to produce enough correctly structured á7 to study.
"You can't study it directly in its natural form, so you have to engineer it," Chen said.
In the case of á7, Chen's collaborator, Dr. Steve Sine from Mayo Clinic, engineered a chimera, a Frankenstein molecule sharing about 70 percent of its structure in common with the á7 that reacted to stimuli in the same way that natural á7 does.
The next step was to form crystals with these proteins for high-resolution study. This turns out to be particularly difficult for neuronal receptors because they are intrinsically flexible — they need to bind to a neurotransmitter, a small molecule that acts as a messenger in the nervous system, and transmit the signal across the protein body. Moreover, these receptors are decorated with sugar molecules that add further flexibility to the system.
The crystallization of á7 was a painstaking process carried out by Shu-xing Li, the first author of the study and a postdoctoral fellow in Chen's lab. For every hundred crystals obtained, only one or two were good enough for structural analysis. Li had to sort through hundreds of crystals to collect enough data for structural analysis.
"In a sense, these crystals are probably among the world's most expensive crystals, certainly more expensive than diamond," Chen said. "But considering the rich information we can get from these crystals about human neuronal receptors, and the potential impact on drug development that can benefit human health, they are worth the effort."
Funding for this research came from USC and the National Institutes of Health.
Robert Perkins | EurekAlert!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences