Sometimes cells resist medication by spitting it back out. Cancer cells, in particular, have a reputation for defiantly expelling the chemotherapy drugs meant to kill them. Researchers at The Rockefeller University have shed new light on a molecular pump that makes this possible, by determining its three-dimensional structure, down to the level of atoms. “This molecular machine ejects numerous anticancer agents, as well as other drugs. However, no one understood how it can recognize and remove such an impressive variety of substances,” says lead researcher Dr. Jue Chen, the William E. Ford Professor and head of the Laboratory of Membrane Biology and Biophysics at The Rockefeller. “By examining how this drug resistant pump binds to its cargo before transporting it, we have found an answer,” she adds. The new structures, described online on February 23, 2017 in Cell, could help to guide the development of more effective treatments for cancer and other disorders. The Cell article is titled “Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1.” Known as MRP1, the pump in question was identified in drug-resistant lung cancer cells in 1992. While some cancer cells express an unusual abundance of this protein, it is also common within normal cells. It’s a part of the barrier that protects the brain from infection, and helps export hormones, immune signaling compounds, and other cargo, including unwanted foreign substances. Unfortunately for modern medicine, MRP1 often mistakes useful chemicals, including opiates, antidepressants, and antibiotics, for potentially harmful ones in need of removal. Proteins charged with transportation across a cell’s membrane tend to be picky, accepting only particular types of cargo, in some cases a single molecule.
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