A new technique for studying proteins
Proteins are vital for life. They only function properly if folded in the correct manner. Other proteins assist in this folding process, which is temperature dependent. A new technique developed by FOM PhD student Rimco Geels, allows the temperature-dependent composition of proteins to be measured extremely accurately using mass spectrometry. This new approach provides biochemists with a valuable tool for studying the behaviour of proteins in greater detail. Geels, who worked at the FOM Institute for Atomic and Molecular Physics in Amsterdam, gained his doctorate from Utrecht University on 28 March 2008.
The folding of protein complexes is controlled by other protein molecules. As correct folding is crucial for the proper functioning of proteins, researchers are very interested in the structure and functioning of the 'helper proteins', so-called chaperones. However, their structure is temperature dependent. Researchers would like to know the exact influence of temperature on the structure of these proteins. Proteins are investigated in the gas phase or in solution. Studying proteins under well-controlled conditions in the complex micro-environment of the human body is still scarcely feasible.
Geels improved a recently developed mass spectrometry technique in such a way that he could set the temperature of the protein solution and keep the molecular structure of the protein intact until the moment of measurement. This allowed him to measure the temperature-dependent composition of the protein with a high degree of precision.
He was also the first to extensively investigate the possibilities for and effects of various gas-phase activation techniques on large protein complexes (see Figures 1 and 2). The purpose of activation is to break the complexes up into smaller pieces, each of which can be precisely distinguished with a mass spectrometer. Researchers can subsequently use such measurements to reconstruct the original structure of the protein complex. Geels' measurements are useful for further studies into the behaviour of other, similar protein structures.
His work provides biochemists with a new, simple and extremely useful method for studying the temperature-dependent behaviour of protein complexes more accurately. This will enable researchers to gain a better understanding of the functioning of proteins.
Geels' work is a typical example of multidisciplinary research. This started in his own research institute (AMOLF), which he entered as a physicist but where he also encountered chemists and biologists in his group. His supervisor, Ron Heeren, became a professor at the Faculty of Chemistry at Utrecht University. Geels was also there on a regular basis to make use of the equipment in the group of chemist Albert Heck and to benefit from his knowledge in measuring proteins. The proteins were supplied by the group of biologist Saskia van der Vies at the Vrije Universiteit Amsterdam, who also contributed her insights to the study. In his thesis Geel stated that "the combination of physics, chemistry and biology yields a multitude of scientific gems".
More information: Rimco Geels, FOM-Institute for Atomic and Molecular Physics (AMOLF), phone +31 (0)20 608 12 34.