2014年6月24日訊 /生物谷BIOON/ --YiiP 是鑲嵌在大腸桿菌細胞膜表面的蛋白，在它的結構中心存在一個鋅離子結合口袋。之前的實驗結果表明，YiiP蛋白通過將一個氫離子轉運進入細胞膜，從而將一個鋅離子運出，研究者假設，該蛋白中存在一個隱藏的轉運通道。
通過一系列的實驗，現在YiiP的轉運機制可以大致描述如下:當細胞膜外面存在大量氫離子而細胞膜內質子濃度很低時，質子濃度形成的濃度差使得氫離子從膜外運輸到膜內，該蛋白的中心口袋向外打開，氫離子結合到其中。由於質子濃度產生的滲透壓村子，蛋白中心結合區域的形狀改變，使得結合口袋向外面部分關閉，向胞內部分打開，之後質子會引發鋅離子到結合口袋的外部。
YiiP蛋白是大腸桿菌中重要的轉運蛋白，控制大腸桿菌體內的鋅離子濃度，鋅離子過高會引起大腸桿菌的死亡。YiiP和人體內的ZnT蛋白非常相似，ZnT蛋白是負責人體內激素分泌和神經信號傳導的重要蛋白。對YiiP蛋白的結構功能研究可能對於藥物的研究提供非常重要的信息。（生物谷Bioon.com）
詳細英文報導：
Certain mutations in one of them, ZnT8, have been associated with an increased susceptibility to type 2 diabetes, but mutations that destroy its function seem to be protective.
A summary of the research will be published online in the journal Nature on June 22.
"Zinc is necessary for life. It requires transporter proteins to get into and out of cells, where it does its work," says Dax Fu, Ph.D., an associate professor of physiology. "If the transporter proteins malfunction, zinc concentrations can reach toxic levels. This study shows us how zinc-removing proteins work."
Zinc is needed to activate genes and to enable many proteins to function. In pancreatic beta cells, high concentrations of zinc are found inside the packages of insulin that they produce, although its precise role there is unknown.
YiiP is found partially embedded in the membranes of the bacterium E. coli, where it has a similar function to the ZnT human proteins. In a previous study, Fu's group mapped YiiP's atomic structure and found that there is a zinc-binding pocket in its center. But how a single pocket could transport zinc from one side of a membrane to the other was a mystery, he says.
Knowing that the protein lets one hydrogen ion -- or proton -- into the cell for every zinc ion it sends out, the team suspected there was a hidden channel that opened up to allow the ions to switch places.
To test this idea and to find out which inner segments of the protein make up the channel, the team collaborated with scientists at Brookhaven National Laboratory to shine intense X-rays at the protein while it was immersed in water. The X-rays caused the water molecules to split into two components: hydrogen atoms and hydroxyl radicals. When the hidden channel within the protein opened up, the hydroxyl radicals bonded with the exposed protein segments, "marking" the ones that created the channel.
The researchers then cut up YiiP using enzymes and analyzed the resulting pieces in an instrument that helped them identify the makeup of each piece. By comparing those pieces to pieces of YiiP that had not been exposed to hydroxyl radicals, the researchers could tell which segments create the channel.
Using this and other information, the scientists were able to figure out how the protein works.
Outside the membrane is an abundance of protons, with a lower concentration inside the membrane, creating what is known as a concentration gradient. The protons want to flow "down" this gradient into the cell, like water following gravity down a waterfall, says Fu. Thus, when the central pocket of the transporter protein is open to the outside, a proton will bind to the pocket.
"When the protons move from a place of high concentration to low concentration, they generate a force like falling water does," he says. The protein harnesses this force to change its shape, cutting off the pocket's access to the outside environment and opening up its access to the inside. There, the proton will continue its "fall" by unbinding from the pocket and entering the inside space.
Once it has released the proton, the pocket is free to bind to zinc. This binding again changes the protein's shape, shutting off the pocket's access to the inside of the membrane and once again exposing it to the outside. A proton then drives the zinc ion out of the pocket, and the cycle continues.
"Understanding the way the protein works, especially which segments of the protein do what, will help us design better drugs to moderate its activity wherever it is found," says Fu.