in three dimensions. Structural biology initiative aims to model membrane protein structures like this.
While people use their eyes and ears for information, cells rely on proteins that cover their outer membranes to search the chemical signals from the outside world. Now, a biotech start-up plans to launch an international consortium to determine the crystal structures in three dimensions 100 such membrane proteins, many of which represent promising drug targets.
Several "structural genomics" efforts have been launched recently to automate the atomic correspondence protein, but this is the first to focus on membrane proteins. The subjects are a class of proteins known as G-protein coupled receptors, which are sensitive to such diverse stimuli as hormones and modified photon pigments. Once these proteins detect a specific signal outside the cell, they give off a cascade of biochemical messengers which modifies the chemical or gene expression in the cell. Scientists would like to know more details, but the receivers are notoriously difficult to work with. Removing them from the cell membrane destroys normal 3D shape and any hope of understanding what they look like in atomic detail.
The consortium, led by start-up Bio-Xtal in Roubaix, France, plans to orchestrate a concerted effort to find new ways to express, crystallize, and the image of the proteins. If all goes as planned, from April the company will work with four university laboratories in France, Germany and the Netherlands. Bio-Xtal has asked the European Union for half the cost estimated at 10 million euros ($ 9.3 million) of the 3-year project, and plans to raise the remainder of pharmaceutical sponsors. Seventeen companies, including Roche, Merck and AstraZeneca, have already offered support, said Etienne The Hermit, the director of Bio-Xtal.
The effort to extend structural genomics of membrane proteins "a great idea," said Aled Edwards, a structural biologist at the University of Toronto. But because membrane proteins are difficult to express and crystallize - two steps to determine their structure - the project is certain to face slow going, he said. "Calling something 'genomics' involves automation and high throughput," says Edwards. In this case, "it is a bit exaggerated."
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