Ras proteins measured for the first time by researchers

For the first time ever a team of biophysicists have successfully measured the orientation of the Ras protein bound to the cell membrane.

Combining the use of three biophysical methods – computer simulations, infrared spectroscopy and fluorescence measurements – the team realised that two Ras molecules form a pair to take an upright position on the membrane.

Previously, it was assumed (based on computer simulations) that the protein is situated horizontally on the membrane as a single molecule.

The Ras protein is the essential "switch" for cell growth and the malfunctioning of it is a significant factor in the development of cancer.

"These results put a completely new light on the nano-cluster formation of Ras at the membrane," said Dr Klaus Gerwert, from the RUB Faculty of Biology and Biotechnology at the University of Bochum.

Results of the study confirmed that the orientation of a protein affects its possible interactions with other proteins.
  
It was also found that Ras molecules are mutually supportive. When there was just one single molecule, it was seen to fall into a horizontal position and lie on the membrane.

Two Ras proteins support each other to keep themselves in the upright position.

Previous studies had shown that Ras molecules are regularly concentrated in small groups (made up of four to ten), named nano-clusters. They also assumed that other proteins have to mediate the formation of clusters.

The team was for the first time able to demonstrate that Ras is actively involved in the process.

"An understanding of the stereo structure of Ras will allow us to adopt novel approaches in drug development," said Klaus Gerwert.

The project was financially supported by the Protein Research Department at RUB, from the State NRW as part of the Centre for Vibrational Microscopy and various other groups.

Posted by Neil Clark