Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Einstein researchers find molecular structure of key fluorescent proteins

23.04.2010
Scientists at Albert Einstein College of Medicine of Yeshiva University have determined the crystal structures of two key fluorescent proteins – one blue, one red – used to “light up” molecules in cells.

That finding has allowed them to propose a chemical mechanism by which the red color in fluorescent proteins is formed from blue. With this information, the researchers now have the first roadmap for rationally designing new and differently colored fluorescent proteins to illuminate the structures and processes in living cells.

Such colored probes could provide a window, for example, into how biological processes in normal cells differ from those in cancer cells. Their study appears in the April 23 print edition of Chemistry & Biology, a Cell Press publication.

This advance will expand the imaging revolution that began with a protein found in jellyfish. In 1992, researchers reported that the gene for green fluorescent protein (GFP) could be fused to any gene in a living cell. When the targeted gene is expressed, a “fusion protein” (consisting of the targeted gene’s protein plus GFP) is formed. This fusion protein exhibits bright green fluorescence when exposed to blue light.

Thanks to GFP, scientists had a green imaging probe offering unprecedented access to the internal workings of living cells. They were able to use high-resolution light (optical) microscopes to observe the activation of genes of interest and to quantify and track newly expressed proteins as they perform their functions in living cells. The 2008 Nobel Prize in Chemistry was awarded to three non-Einstein scientists for their GFP-related discoveries.

Many more fluorescent proteins of various colors were later found in other marine organisms such as corals. But the molecular nature of these colors remained a mystery, hindering the development of new imaging probes. Scientists seeking new fluorescent probes first had to fuse the genes for known fluorescent proteins to bacteria; then they exposed millions of these microorganisms to radiation, in hopes of producing random genetic mutations that lead to new and useful fluorescent proteins. The discovery by Einstein researchers will allow fluorescent proteins to be created in a much more systematic and rational way.

"Knowing the molecular structures of the chromophores – the part of fluorescent protein molecules that gives them their color – we can now do hypothesis-based designing of new probes, instead of relying on random mutations,” says principal investigator Vladislav Verkhusha, Ph.D., associate professor of anatomy and structural biology and member of the Gruss Lipper Biophotonics Center at Einstein.

“In other words,” says Dr. Verkhusha, “if we now change this or that fluorescent protein molecule in a certain way, we can predict that the change will yield a new protein that has a particular fluorescent color or other property that we are interested in.” Using this new information, Dr. Verkhusha’s laboratory has already designed a variety of new fluorescent proteins that can glow in colors ranging from blue to far-red.

Since researchers can now follow only two or three proteins at a time, an expanded fluorescent protein palette would be a big help. “To understand many cellular functions, you would like to follow dozens of different proteins, so the more colors we can develop, the better,” says study co-author Steven C. Almo, Ph.D., professor of biochemistry and of physiology & biophysics at Einstein. He is an expert in x-ray crystallography, a method that determines the arrangement of atoms within a protein by striking the protein crystal with a beam of x rays.

The findings reported in the Chemistry & Biology paper resulted from a multidisciplinary research effort involving Einstein’s Structural Biology Center (where x-ray crystallography studies are carried out) and its Gruss Lipper Biophotonics Center (which develops advanced microscopy techniques to study biological problems related to human disease).

Dr. Verkhusha’s laboratory has also developed new red fluorescent proteins that are photoactivatable, meaning that they can be turned on from the dark to the fluorescent state using a short pulse of light. With these versatile probes, researchers can use real-time super-resolution fluorescence microscopy to capture images as small as 15 to 20 nanometers (the scale of single molecules) in living cells. Before such probes were available, super-resolution fluorescence microscopy could be done only in non-living cells.

Recently, one of Dr. Verkhusha’s photoactivatable probes allowed Einstein scientists to view individual breast cancer cells for several days at a time to obtain new insights into metastasis, the process by which tumor cells spread to other parts of the body. “Mapping the fate of tumor cells in different regions of a tumor was not possible before the development of photoswitching technology,” explains John S. Condeelis, Ph.D., co-chair and professor of anatomy and structural biology, co-director of the Gruss Lipper Biophotonics Center, and the Judith and Burton P. Resnick Chair in Translational Research.

The paper, “Structural characterization of acylimine-containing blue and red chromophores in mTagBFP and TagRFP fluorescent proteins,” is published in the April 23 print edition of Chemistry & Biology (Cell Press). Other Einstein researchers who contributed to the study were Oksana M. Subach, Ph.D., Vladimir N. Malashkevich, Ph.D., Wendy D. Zencheck, Ph.D., Kateryna S. Morozova, M.S., and Kiryl D. Piatkevich, M.S.

Deirdre Branley | EurekAlert!
Further information:
http://www.einstein.yu.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>