Featured Research

from universities, journals, and other organizations

Solving the structure of a protein that shows promise as a DNA-targeting molecule for gene correction, therapy

Date:
January 5, 2012
Source:
Fred Hutchinson Cancer Research Center
Summary:
Researchers have solved the three-dimensional structure of a newly discovered type of gene-targeting protein that has shown to be useful as a DNA-targeting molecule for gene correction, gene therapy and gene modification.

This image represents the structure of a TAL effector protein bound to its DNA target. The protein winds around the outside of the DNA double helix and “reads” the identity of each base. The ability to recognize and bind to a single unique, long DNA sequence allows the protein to act as a highly specific gene-targeting molecule.
Credit: Stoddard laboratory, Fred Hutchinson Cancer Research Center

Researchers at Fred Hutchinson Cancer Research Center have solved the three-dimensional structure of a newly discovered type of gene-targeting protein that has shown to be useful as a DNA-targeting molecule for gene correction, gene therapy and gene modification.

The findings are published online in Science Express on Jan. 5.

Using a unique form of computational and X-ray crystallographic analyses, a team of researchers led by Barry L. Stoddard, Ph.D., a member of the Basic Sciences Division at the Hutchinson Center, has determined the structure of a protein called a "TAL effector," which stands for "transcription-activator-like effector."

"These proteins have a LEGO-like, modular architecture that allows them to easily be reshuffled and engineered for DNA targeting," Stoddard said. "The upcoming years will see an explosion in the development and use of TAL effectors -- and more complicated molecules that are built around TAL structures -- for targeted gene modification, genetic engineering and corrective gene therapy."

TAL proteins exist only in Xanthomonas, a type of gram-negative bacteria that can infect soybeans, tomatoes, peppers, rice and citrus plants, among other species.

Although in nature bacteria use these proteins to target specific sites in plant DNA, they have the potential to be used in a clinical setting to help humans, Stoddard said. "In biotechnology and medicine TAL effectors can be used by scientists to seek out and bind to DNA targets in any organism of choice, including genes in humans that contain disease-causing mutations that we might want to correct," Stoddard said, referring to a field known as "targeted gene correction," which requires the development of molecules that can be delivered directly to a single DNA site. "TAL effectors have this unique capability and can be harnessed for such uses," he said.

Since their discovery, TAL effectors have been intensely studied for gene modification applications and have been commercialized by several companies around the world. "However, until now, the lack of structure has greatly impeded the further development and improvement of TAL effectors for genetic engineering and correction," Stoddard said.

Solving the structure of the TAL effector protein allows scientists to see exactly how the protein binds to its DNA target and exactly what types of contacts it makes to the DNA in order to recognize and "read" each base in the DNA sequence. "By determining the structure, it is now possible to engineer the protein to work more effectively in a variety of biotech or medical applications, either by changing its DNA-targeting specificity, making the protein more stable or longer lived in cells, or by understanding how to attach additional protein modules to it that can drive desired changes in the DNA target," Stoddard said.

The research was conducted in collaboration with computational biologist Philip Bradley, Ph.D., an assistant member of the Hutchinson Center's Public Health Sciences Division, who specializes in the computer modeling of proteins; Amanda Nga-Sze Mak, Ph.D., a postdoctoral fellow in Stoddard's lab; Adam Bogdanove, Ph.D., a professor of plant pathology and microbiology at Iowa State University, who discovered many of the properties of the TAL proteins; and Raul Cernadas, Ph.D., a postdoctoral research associate in Bogdanove's lab. The National Institutes of Health, National Science Foundation, Searles Scholars Fellowship Program and Northwest Genome Engineering Consortium funded the research.


Story Source:

The above story is based on materials provided by Fred Hutchinson Cancer Research Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. N.-S. Mak, P. Bradley, R. A. Cernadas, A. J. Bogdanove, B. L. Stoddard. The Crystal Structure of TAL Effector PthXo1 Bound to Its DNA Target. Science, 2012; DOI: 10.1126/science.1216211

Cite This Page:

Fred Hutchinson Cancer Research Center. "Solving the structure of a protein that shows promise as a DNA-targeting molecule for gene correction, therapy." ScienceDaily. ScienceDaily, 5 January 2012. <www.sciencedaily.com/releases/2012/01/120105141141.htm>.
Fred Hutchinson Cancer Research Center. (2012, January 5). Solving the structure of a protein that shows promise as a DNA-targeting molecule for gene correction, therapy. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2012/01/120105141141.htm
Fred Hutchinson Cancer Research Center. "Solving the structure of a protein that shows promise as a DNA-targeting molecule for gene correction, therapy." ScienceDaily. www.sciencedaily.com/releases/2012/01/120105141141.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

More Coverage


Scientists Find Structure of Gene-Editing Protein

Jan. 5, 2012 In the two and a half years since scientists discovered how a class of proteins find and bind specific sequences in plant genomes, researchers worldwide have moved fast to use this discovery. Now, ... read more
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins