UPTON, NY -- Sometimes a cell has to die-when it's done with its job or inflicted with injury that could otherwise harm an organism. Conversely, cells that refuse to die when expected can lead to cancer. So scientists interested in fighting cancer have been keenly interested in learning the details of "programmed cell death." They want to understand what happens when this process goes awry and identify new targets for anticancer drugs.
The details of one such target have just been identified by a group of scientists from the U.S. Department of Energy's Brookhaven National Laboratory, Columbia University, New York University, Baylor College of Medicine, Technical University of Munich, and the New York Structural Biology Center. The group, known as the New York Consortium on Membrane Protein Structure (NYCOMPS), used x-rays at Brookhaven Lab's National Synchrotron Light Source (NSLS) to decipher the atomic level structure of a protein that regulates the level of calcium in cells. The work is described as a research article published in Science, June 6, 2014.
"The accumulation of calcium is a key signaling agent that can trigger programmed cell death, or apoptosis," explained Wayne Hendrickson of Columbia and Brookhaven, and the director of NYCOMPS as well as a senior author on the paper. "Our study reveals how this protein, embedded in a cellular membrane structure called the endoplasmic reticulum, serves as a molecular safety valve for keeping calcium levels steady. Designing drugs that inhibit this protein would promote cell death, which could be a promising strategy for fighting cancers in which such proteins are overexpressed."
3-D Model for Rational Drug Design
The protein that the scientists studied is a prokaryotic homolog of human "Transmembrane Bax Inhibitor Motif" (TMBIM) proteins, which come in six varieties. TMBIM6 is overexpressed in various cancers-including prostate, breast, glioma, uterine,
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DOE/Brookhaven National Laboratory