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 ë-integrase (ë-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 ë-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.”
Former Brown postdoctoral research associates Marta Radman-Livaja and Sang Yeol Lee were part of the research team, along with Tapan Biswas, a former postdoctoral research associate at Harvard Medical School. Landy, a professor of medical science in Brown’s Department of Molecular Biology, Cell Biology and Biochemistry, acted as senior scientist on the project.
The National Institute of General Medical Sciences supported the work.
Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews and maintains an ISDN line for radio interviews. For more information, call the Office of Media Relations at (401) 863-2476.
Wendy Lawton | EurekAlert!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences