Zurich – Researchers at the Federal Institute of Technology (ETH) in Zurich have developed a new method for crystallizing large membrane proteins. This is necessary to determine their structure, which is important in therapeutics and diagnostics.

Membrane proteins perform a wide range of functions, such as transporting substances into or out of the cell or mediating the immune response. Determining their structure and functions is therefore very important for pharmaceutical research. 

According to an ETH Zurichstatement, it has been very difficult until now to elucidate the structure of membrane proteins as they are insoluble in water and often too large and heterogeneous to be crystallized in the standard method using narrow channels filled with stable water-lipid mixtures.

A group of ETH researchers led by Raffaele Mezzenga, Professor of Food and Soft Materials at ETH Zurich, have now developed a method that makes it possible to crystallize membrane proteins of any type or size. 

The researchers mixed a small proportion of electrically charged lipids in with the regular lipids. These repel one another and thus inflate the channels, providing enough space even for large membrane proteins to embed themselves into the channel walls using the hydrophobic part that otherwise sits in the cell membrane. The rest of the protein ends up in the water channel’s interior and the proteins, once correctly constituted, can then start to crystallize, explains ETH Zurich. 

“This tool will give new impetus to structural elucidation, as it opens up proteins that were previously out of reach,” said Mezzenga. He believes that their research could also be of benefit to the pharmaceutical industry.

“The ability to determine structure is of paramount importance for the development of new drugs,” he added. 

At present, scientists know the exact structure of only about one seventh of all membrane proteins.

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