Computer-designed protein triggers self-destruction of Epstein-Barr-infected cancer cells

June 19, 2014
A small chunk of protein (red) bound to the Epstein-Barr virus target protein (gray) was extended to make a much longer protein, left, and then designed to have a rigid folded structure, right, for tight and specific interactions with the target. Credit: University of Washington

A protein molecule, "BINDI," has been built to trigger self-destruction of cancer cells infected with the Epstein-Barr virus.

Numerous cancers are linked to the Epstein-Barr , which can disrupt the body's weeding of old, abnormal, infected and damaged cells.

The Epstein-Barr virus persists for a long time after a bout with mononucleosis or other diseases for which it is responsible. It survives by preventing cells from disintegrating to kill themselves and their invaders. The virus' interference with cell population control may contribute to cancerous overgrowth.

In a June 19 report in the scientific journal Cell, researchers describe how they computer-designed, engineered and tested a protein that overrides the virus' interference. BINDI, they discovered, can prompt Epstein-Barr-infected cancer cell lines to shrivel, disassemble their components and burst into small pieces.

The BINDI protein was created at the UW Institute for Protein Design. (BINDI is an acronym for BHRF1-INhibiting Design acting Intracellularly.)

Lead authors of the paper are Erik Procko of the Department of Biochemistry and Geoffrey Y. Berguig of the Department of Bioengineering, both at the University of Washington. They collaborated with scientists and clinicians at the UW, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance and Scripps Research Institute.

The research team also tested the protein in a laboratory model of Epstein-Barr virus-positive lymphoma. Lymphoma is a type of cancer that can affect the lymph nodes, spleen, bone marrow, blood and other areas of the body. The researchers grafted lymphoma tissue onto mice as a living system to evaluate BINDI's therapeutic properties.

The scientists delivered the protein into via an antibody-targeted nanocarrier newly designed to deliver protein cargo to intracellular cancer targets. BINDI behaved as ordered: It suppressed tumor growth and enabled the mice to live longer.

"We are especially interested in designing proteins that selectively kill targeted cells," the researchers noted, "because they may provide advantages over current compounds that are toxic to other cells."

The work also demonstrates the potential to develop new classes of intracellular protein drugs, as current protein therapeutics are limited to extracellular targets.

BINDI was designed to recognize and attach itself to an Epstein-Barr virus protein called BHRF1, and to ignore similar proteins. BHRF1 keeps cancer cells alive, but when bound to BINDI, it can no longer fend off cell death.

By examining the crystal structure of BINDI, the scientists saw that it nearly matched their computationally designed architecture for the .

"This close agreement between the model and the actual structure highlights the success in which designer toxins can be developed," the researchers said.

Explore further: Young killer cells protect against infectious mononucleosis

Related Stories

Young killer cells protect against infectious mononucleosis

December 19, 2013
More than 90 percent of all adults are carriers of the oncogenic Epstein-Barr Virus (EBV). Primary infection with this herpes virus as a young child is generally not linked to any symptoms, and usually offers life-long protection ...

Researchers discover how the kissing disease virus hijacks human cells

April 10, 2014
University of Montreal researchers have discovered how a component of the Epstein Barr (EBV) virus takes over our cells gene regulating machinery, allowing the virus to replicate itself. The EBV virus causes a variety of ...

Researchers reveal how a protein common in cancers jumps anti-tumor mechanisms

March 17, 2014
A Stony Brook University-led international team of infectious disease researchers have discovered how a cellular protein, called STAT3, which is overactive in a majority of human cancers, interferes with an antitumor mechanism ...

Researchers find Epstein Barr-like virus infects and may cause cancer in dogs

March 12, 2012
More than 90 percent of humans have antibodies to the Epstein Barr virus. Best known for causing mononucleosis, or "the kissing disease," the virus has also been implicated in more serious conditions, including Hodgkin's, ...

Immune system discovery could lead to EBV vaccine to prevent mono, some cancers

October 11, 2013
Development of a vaccine against Epstein-Barr virus (EBV) has taken a step forward with the Canadian discovery of how EBV infection evades detection by the immune system.

Recommended for you

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

0 comments

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.