Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Improved molecular switch could serve as sensor, medical tool

30.11.2004


’Device’ made of fused protein partners is shown to be reversible and highly sensitive



Improving significantly on an early prototype, Johns Hopkins University researchers have found a new way to join two unrelated proteins to create a molecular switch, a nanoscale "device" in which one biochemical partner controls the activity of the other. Lab experiments have demonstrated that the new switch performs 10 times more effectively than the early model and that its "on-off" effect is repeatable.

The new technique to produce the molecular switch and related experimental results are reported in the November issue of the journal Chemistry & Biology. The paper builds on earlier research, led by Marc Ostermeier, which demonstrated that it was possible to create a fused protein in which one component sends instructions to the other. The second then carries out the task. "Last year, we reported that we’d used protein engineering techniques to make a molecular switch, putting together two proteins that normally had nothing to do with one another, but the switching properties of that version were insufficient for many applications," said Ostermeier, an assistant professor in the Department of Chemical and Biomolecular Engineering at Johns Hopkins. "With the new technique, we’ve produced a molecular switch that’s over 10 times more effective. When we introduce this switch into bacteria, it transforms them into a working sensor."


As in their earlier experiments, Ostermeier’s team made a molecular switch by joining two proteins that typically do not interact: beta-lactamase and the maltose binding protein found in a harmless form of E. coli bacteria. Each of these proteins has a distinct activity that makes it easy to monitor. Beta-lactamase is an enzyme that can disable and degrade penicillin-like antibiotics. Maltose binding protein binds to a type of sugar called maltose that E. coli cells can use as food.

In the previous experiments, the researchers used a cut-and-paste process to insert the beta-lactamase protein into a variety of locations on the maltose binding protein, both proteins being long chains of amino acids that can be thought of as long ribbons. In the new process, the team joined the two natural ends of the beta-lactamase chain to create one continuous molecular loop. Then, they snipped this "ribbon" at random points before inserting the beta-lactamase in random locations in the maltose binding protein. This technique, called random circular permutation, increases the likelihood that the two proteins will be fused in a manner in which they can communicate with each other, Ostermeier said. As a result, it’s more likely that a strong signal will be transmitted from one partner to the other in some of the combined proteins.

In their new paper, the Johns Hopkins team reported that this technique yielded approximately 27,000 variations of the fused proteins. Among these, they isolated one molecular switch, in which the presence of maltose, detected by one partner, caused the other partner to increase its attack on an antibiotic 25-fold. They also showed that the switch could be turned off: When the maltose triggering agent was removed, the degradation of the antibiotic instantly slowed to its original pace.

Ostermeier believes the same molecular switch technology could be used to produce "smart" materials, medical devices that can detect cancer cells and release drugs, and sensors that could sound an alarm in the presence of chemical or biological agents. His team is now seeking to create a molecular switch that fluorescently lights up only in the presence of certain cellular activity. "We’ve proven that we can make effective molecular switches," he said. "Now, we want to use this idea to create more interesting and more useful devices."

Gurkan Guntas, a doctoral student in Ostermeier’s lab, was lead author on the new Chemistry & Biology paper. The co-authors were Ostermeier and Sarah F. Mitchell, a doctoral student in the Program in Molecular Biophysics at Johns Hopkins. The research was supported by a grant from the National Institutes of Health. The Johns Hopkins University has applied for a patent covering the molecular switch and methods of producing it.

Phil Sneiderman | EurekAlert!
Further information:
http://www.jhu.edu

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>