Featured Research

from universities, journals, and other organizations

Cancer researchers find key protein link

Date:
March 27, 2014
Source:
Rice University
Summary:
A new understanding of proteins at the nexus of a cell's decision to survive or die has implications for researchers who study cancer and age-related diseases. Experiments and computer analysis of two key proteins revealed a previously unknown binding interface that could be addressed by medication.

A combination of experimental and theoretical studies, in particular direct coupling analysis, revealed detailed interactions between NAF-1 (magenta) and Bcl-2 (blue), two proteins involved in cellular life-and-death decisions.
Credit: Mark Paddock, Patricia Jennings/UCSD

A new understanding of proteins at the nexus of a cell's decision to survive or die has implications for researchers who study cancer and age-related diseases, according to biophysicists at the Rice University-based Center for Theoretical Biological Physics (CTBP).

Experiments and computer analysis of two key proteins revealed a previously unknown binding interface that could be addressed by medication. Results of the research appear this week in an open-source paper in the Proceedings of the National Academy of Sciences.

The proteins are Bcl-2, well-known for its role in programmed cell death, and NAF-1, a member of the NEET family that binds toxic clusters of iron and sulfur. How the two interact is now known as a major determinant in the cell processes of autophagy and apoptosis -- literally, life and death. An ability to uncover binding sites on the proteins that send the cell one way or the other opens a path toward the regulation of those processes, according to José Onuchic, Rice's the Harry C. and Olga K. Wiess Chair of Physics and professor of physics and astronomy.

Pockets and folds in proteins exist to bind to other molecules and catalyze actions in a cell in signaling pathways. The ability to block a specific binding site or to enhance a desired interaction is critical to drug design, Onuchic said.

"In our early work we have shown the link between NEET proteins and cancer. Now we can understand the molecular details of how these interactions are governed," Onuchic said. "Others have shown that NAF-1 is up-regulated in cancer cells, which leads us to believe that cancer may hijack control over the expression of this protein. This affects the cell's system of checks and balances. Understanding NAF-1 gives us a better idea of how to approach treatment."

The researchers found that NAF-1 binds to two specific regions of the protein Bcl-2 and that Bcl-2 binds to the NAF-1 groove formed between the beta cap and iron-sulfur cluster binding domains; the strongest coupling is at the cluster binding domain and some contacts of interest are at the top of the beta-cap domain. Since the iron-sulfur cluster is the functional entity involved in NAF-1 activity, these findings clearly indicate that Bcl-2 interaction with NAF-1 affects its activity, Onuchic said.

The research team used a unique combination of experimental and theoretical methods, including peptide array binding studies with fragments of Bcl-2 to NAF-1; the researchers performed functional studies of cluster transfer and other full-length protein interactions with a spectrometer sensitive to hydrogen/deuterium exchange. They combined their results with a computer-based process created at CTBP called direct coupling analysis (DCA), through which interactions between proteins can be predicted by their genomic roots.

"Each of the three techniques not only confirmed the results of the other methods but also provided unique insights in their own right," said Patricia Jennings, a lead author and CTBP affiliate based at the University of California, San Diego (UCSD), where she is a professor of chemistry and biochemistry.

Jennings said the combined techniques are applicable to biomolecular interactions in general. "DCA helps us efficiently filter through massive amounts of data and does not require high-resolution structural studies, although those are desirable," she said. "Peptide array is powerful for localizing fragments that bind with high affinity, and hydrogen/deuterium exchange studies allow us to monitor parts of the intact protein that are not seen in structural studies and are not amenable to DCA analysis.

"Together, the techniques provide an exquisite synergy," she said.

Jennings is a co-lead author of the study with Onuchic; Rachel Nechushtai, a professor at the Alexander Siberman Life Science Institute of the Hebrew University of Jerusalem; Assaf Friedler, a professor at the Hebrew University Institute of Chemistry; and Ron Mittler, a professor of biological sciences at the University of North Texas, Denton (UNT). Previous research by the team identified NAF-1 as one of two prime suspects in the proliferation of breast cancer.

"Once again, our international team of experts from different disciplines has shown that combined complementary efforts leads to innovative knowledge imperative for coping with cancer," Nechushtai said.


Story Source:

The above story is based on materials provided by Rice University. The original article was written by Mike Williams. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. Tamir, S. Rotem-Bamberger, C. Katz, F. Morcos, K. L. Hailey, J. A. Zuris, C. Wang, A. R. Conlan, C. H. Lipper, M. L. Paddock, R. Mittler, J. N. Onuchic, P. A. Jennings, A. Friedler, R. Nechushtai. Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1403770111

Cite This Page:

Rice University. "Cancer researchers find key protein link." ScienceDaily. ScienceDaily, 27 March 2014. <www.sciencedaily.com/releases/2014/03/140327140059.htm>.
Rice University. (2014, March 27). Cancer researchers find key protein link. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2014/03/140327140059.htm
Rice University. "Cancer researchers find key protein link." ScienceDaily. www.sciencedaily.com/releases/2014/03/140327140059.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) — The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) — Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) — A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) — The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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