What is the largest known membrane protein

10.06.2008 08:26

Membrane proteins produced artificially

Dr. Anne Hardy Marketing and communication
Johann Wolfgang Goethe University Frankfurt (Main)

Mimicking bacterial production machinery in the test tube / Selective labeling of large proteins for NMR

FRANKFURT. The proteins in cell membranes, despite their great importance as an interface between the cell and its environment, are among the least researched proteins. The reason for this is an enveloping layer of fat molecules and their insolubility in water. Both of these make it difficult to investigate with the biophysical methods that have been used up to now. In particular, however, the production of membrane proteins is extremely problematic because, like water-soluble proteins, they often cannot be produced by bacteria. Biochemists at the Institute for Biophysical Chemistry at the University of Frankfurt have now succeeded in establishing a new method for the production of membrane proteins. This allows the proteins to be produced in large enough quantities for an examination. The Frankfurt researchers expect important impulses for pharmaceutical research, because around 60 percent of all drugs act on membrane proteins.

The core of the technology is based on the reproduction of the bacterial production machinery in the test tube, as the researchers report in the "Proceedings of the National Academy of Sciences". The process known as cell-free protein synthesis was developed back in the 1980s, but has only ever been used for water-soluble proteins. Dr. Frank Bernhard from the Institute for Biophysical Chemistry was able to show that this process can be used excellently for the production of a large number of membrane proteins. However, the method also allows completely new approaches to be taken in determining the three-dimensional structure of membrane proteins. For example, biophysicists in the working groups of Prof. Volker Dötsch (Institute for Biophysical Chemistry, Principal Investigator of the Macromolecular Complexes Cluster of Excellence) and Prof. Peter Güntert (Institute for Biophysical Chemistry and Frankfurt Institute for Advanced Studies, FIAS) developed a new method with which Help also larger membrane proteins can be examined more easily in the future.

This method is based on making certain areas of the proteins selectively visible for investigation by means of nuclear magnetic resonance spectroscopy (NMR). The prerequisite for this is the incorporation of certain NMR-active isotopes. The newly developed process uses the great flexibility of cell-free protein synthesis to only mark certain building blocks of the proteins with these NMR-active isotopes, but to leave the rest unmarked. Larger membrane proteins can now also be investigated, the NMR analysis of which has been hampered by the complexity of the spectra so far. With the help of this method, it has now been possible to obtain the first structural information on part of the membrane protein presenilin-1, which is one of the key proteins in the development of Alzheimer's disease. Further applications of the developed technology for the structural analysis of central proteins from the human cardiovascular system are currently being tested at the Institute for Biophysical Chemistry.

Prof. Volker Dötsch, Tel .: (069) 798-29631, [email protected], Institute for Biophysical Chemistry, Principal Investigator Cluster of Excellence Macromolecular Complexes, Campus Riedberg, University of Frankfurt.

GOETHE-UNIVERSITÄT is a strong research university in the European financial metropolis of Frankfurt. Founded 94 years ago by Frankfurt citizens, it is now one of the ten largest universities in Germany. On January 1, 2008, when it returned to its historical roots as a foundation university, it gained a unique degree of independence. Germany's most beautiful campus is currently being built around the historic Poelzig ensemble in Frankfurt's Westend for around 600 million euros. With 34 endowed professorships acquired since 2000, GOETHE-UNI holds the top position in Germany. In three consecutive CHE research rankings and in the Excellence Initiative, GOETHE-UNI is one of the strongest research universities.

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Editor: Dr. Anne Hardy, Science Communication Officer
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Features of this press release:
Biology, chemistry
research results