In a new study, researchers from the Columbia University Medical Center obtained a detailed structural picture of a membrane pore that allows epithelial cells to absorb calcium ions for the first time. This finding may accelerate the development of medicines that correct abnormal calcium intake associated with breast, endometrial, prostate and colon cancers. Relevant research results published in the Journal of Nature.
Although most of the calcium in the body is found in the form of minerals in minerals, the amount of this chemical element that is transported into the cell as ions is carefully controlled. Calcium ions play a crucial role in the regulation of cell function. Cells regulate calcium uptake through special membrane pores or channels that can be opened and closed as needed. TRPV6 is a protein channel located in the intestinal epithelial cell membrane that promotes the uptake of calcium in the diet. Abnormal function of TRPV6 channels may promote cancer by disrupting the control of cell proliferation and cell death.
These researchers use advanced cryogenic electron microscopy to image TRPV6. Cryo-electron microscopy is an imaging technique that combines the images of thousands of frozen molecules into a fine three-dimensional image.
By comparing the structure of the channel protein TRPV6 in the open and closed states, these researchers were able to determine that the core portion of the channel protein, the four closely spaced helical protein fragments, undergoes a slight twist, allowing TRPV6 to open.
Alexander I. Sobolevsky, MD, associate professor of biochemistry and molecular biophysics at the Columbia University Medical Center, said: "We found that this calcium channel opens as a reaction to changes in the middle of each core helix, resulting in These protein fragments bend and rotate outwards enough to create a sufficiently wide opening that allows calcium to pass through. "
When the cells need to be provided with calcium ions, this channel protein can quickly and quickly switch between open and closed states.
Sobolevsky said: "Our findings will help us to better understand how changes in the TRPV6 pathway lead to human diseases such as cancer and provide a template for developing drugs to correct these abnormalities." We will look forward to the further update and application of this new findings.
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