Case Western Reserve University scientists have discovered how a family of proteins—cation diffusion facilitators (CDFs)—regulates an important cellular cycle where a cell’s energy generated is converted to necessary cellular functions. The finding may inform future research aimed at identifying ways to ensure the process works as designed and could lead to significant breakthroughs in the treatment of Parkinson’s disease, chronic liver disease, and heart disease. The results of this research were posted online recently by the journal Nature.
“CDF is a major protein family type found in all forms of life,” says senior author Mark R. Chance, PhD. “Mutations or altered regulation of human CDFs modify the concentrations of metal ions critical to cell function and are associated with key human diseases, including those affecting endocrine, neurologic, hepatic, and cardiovascular systems.”
Chance and his colleagues studied a form of CDF found in bacteria where the protein YiiP functions like a motor, using energy in the form of a gradient of protons (hydrogen atoms) to pump zinc ions out of cells. While zinc is pushed successfully out of the cell, a flow of protons is pulled into it. A perfectly functioning zinc-proton flow cycle, then, brings in protons, which the YiiP protein converts into conformational changes in the protein structure. Those changes, in turn, send zinc out of the cell. If the CDF-regulated gate controlling the zinc-proton cycle malfunctions, a range of diseases can result.
To visualize the zinc-proton cycle, researchers used sophisticated dynamic imaging technology as well as mass spectrometry to study the labeled proteins. These technologies allowed investigators to watch the YiiP protein in real time as it took up zinc atoms and rearranged its structure cycle through a pumping sequence. Read the article preview.
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