Einstein College researchers determine molecular structure of key fluorescent proteins

Bronx, NY--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 for optical molecular imaging (OMI). The finding allows 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.

"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, associate professor of anatomy and structural biology and member of the Gruss Lipper Biophotonics Center at Einstein. "In other words," says 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, Verkhusha's laboratory has already designed a variety of new fluorescent proteins that can glow in colors ranging from blue to far-red.

For the full story, go to www.einstein.yu.edu/home/news.asp?id=487.

--Posted by Gail Overton; [email protected]; www.laserfocusworld.com.