Brown scientists map structure of DNA-doctoring protein complex

December 6, 2006
DNA dressed for a party
The three-dimensional representation of a DNA-protein complex, developed through fluorescence resonance energy transfer, helped scientists understand the process whereby mobile DNA inserts itself into a chromosome. Image: Marta Radman-Livaja

More than half of the human genome is made up of bits of mobile DNA, which can travel inside the body and insert genes into the chromosomes of target cells. This DNA doctoring not only shapes species over time, it also spreads antibiotic resistance and is used by bacteria that spread Lyme disease and by viruses linked to certain forms of cancer.

Last year in Nature, scientists working in the Brown University lab of Arthur Landy and the Harvard Medical School lab of Thomas Ellenberger announced they had solved the structure of "-integrase ("-Int), the protein "surgeon" that allows mobile DNA to cut into a chromosome, insert its own genes, and then sew the chromosome back up. That work was conducted using the lambda virus, which infects Escherichia coli (E. coli) bacteria and serves as a model that scientists use to understand mobile DNA.

Now scientists in the Landy lab have solved the structure of a DNA-protein complex that acts as a team of "nurses," aiding "-Int during this snip-and-solder procedure known as site-specific recombination. The structure is a three-dimensional representation of the DNA within this complex. Pictured on the cover of the Nov. 17, 2006, journal Molecular Cell, it looks like DNA dressed for a party, a double helix decked with clumps of curly, colorful ribbon. By solving this structure, scientists now know how these six proteins interact with each other and fold DNA during site-specific recombination.

"Once you know how these proteins and DNA are arranged, you have a much better sense of their function," said Xingmin Sun, a postdoctoral research associate in the Landy lab and the lead author of the journal article. "And once you know their function, you begin to see how the real work inside cells gets done."

Sun said solving the structure of the DNA-protein complex called for some creativity. Because it is a string of six proteins, the complex is too big and too flexible to analyze through standard methods such as X-ray crystallography.

Sun used fluorescence resonance energy transfer or FRET, a technique typically used to study small protein complexes in a solution. This time, Sun used FRET to study large protein complexes in a gel. He tagged the DNA with fluorescent dyes and purified the proteins, placing them in a gel that was then shot through with light. Sun measured the wavelengths of light as they bounced between the molecules of dye. Those measurements were then fed into a special software program created by Dale Mierke, a Brown professor of medical science, which plotted their positions to create the structural map.

"The real breakthrough here is successfully using FRET to determine the structure of a large protein-DNA complex," Sun said. "Biologists now have a new tool to help them understand a variety of these complexes, including ones that control cell division, gene expression and DNA replication. So this technique represents a big advance."

Source: Brown University

Explore further: Method enables researchers to sequence complex sugar molecules for the first time

Related Stories

Study adds to evidence that viruses are alive

September 25, 2015

A new analysis supports the hypothesis that viruses are living entities that share a long evolutionary history with cells, researchers report. The study offers the first reliable method for tracing viral evolution back to ...

DNA-based nanodevices for molecular medicine

September 24, 2015

Researchers from Aalto University have published an article in the recent Trends in Biotechnology journal. The article discusses how DNA molecules can be assembled into tailored and complex nanostructures, and further, how ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.