Release date: 2018-01-02
In a new study, researchers from the Columbia University Medical Center for the first time obtained a detailed structural picture of a membrane pore that allows epithelial cells to absorb calcium ions. This finding may accelerate the development of drugs that correct for abnormal calcium uptake associated with breast, endometrial, prostate, and colon cancers. The relevant research results were published online in the Nature Journal on December 20, 2017, and the title of the paper is "Opening of the human epithelial calcium channel TRPV6".
The TRPV6 channel is open and closed, the picture is from Sobolevsky lab/CUMC.
Although most of the calcium in the human body is present in the bone in the form of minerals, the amount of this chemical element transported to the cells in ionic form is carefully controlled. Calcium ions play a crucial role in regulating cell function. The cells regulate calcium uptake by a special membrane pore or channel that can be opened and closed as needed. TRPV6 is a protein channel located in the epithelial cell membrane of the intestinal wall that promotes the intake of calcium ions in the diet. Abnormal function of the TRPV6 channel may promote cancer production by disrupting control of cell proliferation and cell death.
These researchers used advanced cryo-electron microscopy to image TRPV6. Cryogenic electron microscopy is an imaging technique that combines 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 this channel protein, the four closely-arranged helical protein fragments, was slightly distorted, allowing TRPV6 to open.
Dr. Alexander I. Sobolevsky, associate professor of biochemistry and molecular biophysics at Columbia University Medical Center, said, "We found that this calcium channel opens in response to changes in the middle part of each core helix, resulting in These protein fragments bend and rotate outward, which is enough to create a wide enough opening to allow calcium ions to pass through."
This channel protein is able to switch between an open state and a closed state quickly and quickly when it is desired to provide calcium ions to the cells.
Dr. Sobolevsky said: "Our findings will help us better understand how changes in TRPV6 channels lead to human diseases such as cancer, and provide a template for developing drugs to correct these abnormalities."
Source: Bio Valley
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