News – In 1986, Kazumitsu Ueda’s cell biochemist, currently at the Kyoto University Institute for Integrated Cell Material Sciences (iCeMS), discovered that a protein called ABCB1 could carry multiple chemotherapeutics out of some cells cancer, making them resistant to treatment. How he has done this has remained a mystery for the past 35 years. Now, his team has published a review in the magazine FEBS letters, summarizing what they have learned after years of study on this and other ATP-binding (ABC) transport proteins.
ABC transport proteins are very similar across species and have several transport functions: induction of nutrients into cells, export of toxic fertilizers outside them, and regulation of lipid density within cell membranes.
ABCB1 is one of these proteins, and is responsible for the excretion of toxic fertilizers from the cell in vital organs such as the brain, testes, and placenta. Occasionally, however, it can also remove chemotherapeutic drugs from cancer cells, making them resistant to treatment. The protein lies across the cell membrane, with one end reaching into the cell and the other sticking out into the surrounding area. Even though scientists have known its functions and structure for years, it is not clear how it will work.
Ueda and his team made crystals on the ABCB1 protein before and after export. They then performed X-ray experiments to determine the differences between the two structures. They also performed analyzes using ABCB1 bound with fluorescent proteins to monitor the conformal changes during transport.
They found that fertilizers that are supposed to be absorbed enter the ABCB1 cavity through a gate in the part of the protein that lies inside the cell membrane. The manure lies at the top of the cave, where it binds to molecules, causing a structural change in the protein. This change requires energy, which is obtained from the adenosine triphosphate (ATP) molecules. When magnesium ions bind to ATP, the part of ABCB1 inside the cell packs in on itself and tightens, causing the cavities to shrink and then collapse. closing. This opens the exit gate of the protein. ATP is also involved in the gradual production of ABCB1 from bottom to top, leading to a twisting and squeezing movement that expels the fertilizer into the extracellular space.
“This equipment is different from the other transport proteins,” Ueda says. “We expect our work to help study other ABC proteins, such as those involved in cholesterol homeostasis.”
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About Kyoto University Institute for Integrated Cell Material Sciences (iCeMS):
At iCeMS, our mission is to explore the mysteries of life by creating fertilizers to control cells, and further down the road to create life – inspired substances.
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