Nanotechnology Now

Our NanoNews Digest Sponsors


Heifer International

Wikipedia Affiliate Button

Home > Press > Cell growth protein forms a “pair” on the cell membrane

Abstract:
Upright instead of horizontal

Cell growth protein forms a "pair" on the cell membrane

Bochum und Dortmund researchers measure the orientation of Ras proteins

Cell growth protein forms a “pair” on the cell membrane

Bochum, Germany | Posted on October 16th, 2012

Bochum biophysicists in collaboration with the MPI Dortmund have for the first time measured the orientation of the Ras protein bound to the cell membrane. The RUB team combined the use of three biophysical methods - infrared spectroscopy, computer simulations and fluorescence measurements - and came to the surprising conclusion that two Ras molecules form a pair to take an upright position on the membrane. It was previously assumed, based on computer simulations, that the protein is located horizontally on the membrane as single molecule. Ras is the central "switch" for cell growth, and malfunction of this protein is an important factor in the development of cancer. "These results put a completely new light on the nano-cluster formation of Ras at the membrane," said Professor Dr. Klaus Gerwert from the RUB Faculty of Biology and Biotechnology. The study was chosen as the cover story for the Biophysical Journal.

Orientation affects protein interactions

The orientation of a protein affects its possible interactions with other proteins. "This is similar to comparing the situations of a guest being welcomed with open arms and the host lying on the couch during the greeting," illustrates Dr. Jörn Güldenhaupt, who conducted the orientation measurements. Few biophysical methods allow the protein orientation to be determined. ATR-FTIR spectroscopy, which has been established by the Chair for Biophysics, is one of them.

Ras molecules are mutually supportive

The false assumption that Ras lies on the membrane was based on earlier computer simulations. Till Rudack from the Bochum research team also took a virtual look at Ras. The result: A single upright Ras molecule very quickly falls over and seems to lie on the membrane. "Something must have supported the Ras in our measurements," said Till Rudack. "And that could only be another Ras molecule that was not present in the simulation." In fact, further computer simulations of two mutually supportive Ras molecules yielded a stable upright orientation - which would fit the experimental results.

Fluorescence resonance energy transfer: a molecular yardstick

The team confirmed the results with another piece of experimental evidence using "FRET" (fluorescence resonance energy transfer). This is currently the best method for detecting interactions between two proteins. Here, researchers mark the Ras proteins with two different dyes. If the proteins interact, they are very close together so that energy is transferred from the one dye to the other. As with a yardstick, the distance between the proteins can be measured from the ratio of the transferred energy. For the Ras-Ras interaction, the biophysicists determined a distance of 4.6 nanometres, or millionths of a millimetre. This corresponded exactly to the distance they had predicted with their computer simulations for a "double-Ras".

Stronger in the group

Earlier studies had shown that Ras molecules are often concentrated in small groups. These so-called nano-clusters consist of four to ten Ras proteins. Up until now, it was assumed that other proteins have to mediate the formation of clusters. "We were able to demonstrate for the first time that Ras itself is actively involved," said Dr. Carsten Kötting, an Assistant Professor. The clustering is a great advantage for Ras. The proteins are able to pass on a signal more clearly in the group, i.e. with fewer errors. The SOS protein, for example, always transmits one signal simultaneously to two Ras molecules. If Ras is present in a double form (as a dimer), this step is much easier. An understanding of the stereo structure of Ras will allow us to adopt novel approaches in drug development. "So far, no drugs have been discovered which act directly on Ras," said Klaus Gerwert. "Ras is to be considered undruggable. The Ras-Ras interface could be a new starting point, however, in the development of Ras drugs."

Project grant

Financial support for the project has come from the Protein Research Department at RUB, from the State NRW as part of the Centre for Vibrational Microscopy (CVM) and from SFB 642 "GTP and ATP-dependent membrane processes" (Professor Gerwert is their spokesperson).

Full bibliographic information

J. Güldenhaupt, T. Rudack, P. Bachler, D. Mann, G. Triola, H. Waldmann, C. Kötting, K. Gerwert (2012): N-Ras forms dimers at POPC membranes, Biophysical Journal, doi: 10.1016/j.bpj.2012.08.043

Editor: Dr. Julia Weiler

####

About Ruhr-Universitaet-Bochum
The sixth largest university in Germany.

For more information, please click here

Contacts:
Prof. Dr. Klaus Gerwert
Chair for Biophysics
Faculty of Biology and Biotechnology
Ruhr-Universität
44780 Bochum, Germany
Tel. +49/234/32-24461

Copyright © AlphaGalileo

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Ageing can drive progress: Population ageing is likely to boost medicine, nanotechnology and robotics, but increase political risks July 27th, 2016

WSU researchers 'watch' crystal structure change in real time: Breakthrough made possible by new Argonne facility July 27th, 2016

Enhancing molecular imaging with light: New technology platform increases spectroscopic resolution by 4 fold July 27th, 2016

New nontoxic process promises larger ultrathin sheets of 2-D nanomaterials July 27th, 2016

Imaging

WSU researchers 'watch' crystal structure change in real time: Breakthrough made possible by new Argonne facility July 27th, 2016

Enhancing molecular imaging with light: New technology platform increases spectroscopic resolution by 4 fold July 27th, 2016

Govt.-Legislation/Regulation/Funding/Policy

WSU researchers 'watch' crystal structure change in real time: Breakthrough made possible by new Argonne facility July 27th, 2016

Enhancing molecular imaging with light: New technology platform increases spectroscopic resolution by 4 fold July 27th, 2016

New nontoxic process promises larger ultrathin sheets of 2-D nanomaterials July 27th, 2016

Scientists test nanoparticle drug delivery in dogs with osteosarcoma July 26th, 2016

Nanomedicine

Scientists test nanoparticle drug delivery in dogs with osteosarcoma July 26th, 2016

The NanoWizard® AFM from JPK is applied for interdisciplinary research at the University of South Australia for applications including smart wound healing and how plants can protect themselves from toxins July 26th, 2016

Accurate design of large icosahedral protein nanocages pushes bioengineering boundaries: Scientists used computational methods to build ten large, two-component, co-assembling icosahedral protein complexes the size of small virus coats July 25th, 2016

New superconducting coil improves MRI performance: UH-led research offers higher resolution, shorter scan time July 23rd, 2016

Discoveries

WSU researchers 'watch' crystal structure change in real time: Breakthrough made possible by new Argonne facility July 27th, 2016

Enhancing molecular imaging with light: New technology platform increases spectroscopic resolution by 4 fold July 27th, 2016

New nontoxic process promises larger ultrathin sheets of 2-D nanomaterials July 27th, 2016

Scientists test nanoparticle drug delivery in dogs with osteosarcoma July 26th, 2016

Announcements

Ageing can drive progress: Population ageing is likely to boost medicine, nanotechnology and robotics, but increase political risks July 27th, 2016

WSU researchers 'watch' crystal structure change in real time: Breakthrough made possible by new Argonne facility July 27th, 2016

Enhancing molecular imaging with light: New technology platform increases spectroscopic resolution by 4 fold July 27th, 2016

New nontoxic process promises larger ultrathin sheets of 2-D nanomaterials July 27th, 2016

Tools

WSU researchers 'watch' crystal structure change in real time: Breakthrough made possible by new Argonne facility July 27th, 2016

Enhancing molecular imaging with light: New technology platform increases spectroscopic resolution by 4 fold July 27th, 2016

Nanometrics Reports Second Quarter 2016 Financial Results July 26th, 2016

The NanoWizard® AFM from JPK is applied for interdisciplinary research at the University of South Australia for applications including smart wound healing and how plants can protect themselves from toxins July 26th, 2016

Grants/Awards/Scholarships/Gifts/Contests/Honors/Records

Scientists test nanoparticle drug delivery in dogs with osteosarcoma July 26th, 2016

Ultra-flat circuits will have unique properties: Rice University lab studies 2-D hybrids to see how they differ from common electronics July 25th, 2016

Accurate design of large icosahedral protein nanocages pushes bioengineering boundaries: Scientists used computational methods to build ten large, two-component, co-assembling icosahedral protein complexes the size of small virus coats July 25th, 2016

New reaction for the synthesis of nanostructures July 21st, 2016

Nanobiotechnology

Scientists test nanoparticle drug delivery in dogs with osteosarcoma July 26th, 2016

Accurate design of large icosahedral protein nanocages pushes bioengineering boundaries: Scientists used computational methods to build ten large, two-component, co-assembling icosahedral protein complexes the size of small virus coats July 25th, 2016

New remote-controlled microrobots for medical operations July 23rd, 2016

Nanoparticle versus cancer: Scientists have created nanoparticles which cure cancer harmlessly July 22nd, 2016

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







Car Brands
Buy website traffic