?美國(guó)Stanford同步加速輻射實(shí)驗(yàn)室（SSRL）的科學(xué)家最近發(fā)現(xiàn)了結(jié)核桿菌控制銅代謝的蛋白的基因,。銅是生物必不可少的一種元素,，但是其含量必須受到嚴(yán)格控制,，因?yàn)檫^(guò)量的銅會(huì)導(dǎo)致細(xì)胞死亡?？茖W(xué)家將研究結(jié)果發(fā)表在明年1月的《Nature Chemical Biology》上,，文章說(shuō)明了細(xì)菌是怎樣控制銅的含量的，而這可能發(fā)現(xiàn)治療肺結(jié)核的新方法,。
??這一研究小組由Texas A&M大學(xué)的David Giedroc領(lǐng)導(dǎo),，他們發(fā)現(xiàn)多種細(xì)菌中都有基因CsoR，這能制造和銅結(jié)合的蛋白質(zhì),。Giedroc說(shuō)：“金屬離子例如銅是很多致病生物的弱點(diǎn),，高濃度的這些離子是致命的,，但是細(xì)胞又需要這些離子保護(hù)蛋白質(zhì)，DNA等,。”
??通過(guò)這些蛋白質(zhì)可以保護(hù)細(xì)菌免受銅離子的傷害,，但是產(chǎn)生這些蛋白質(zhì)的基因以及這些蛋白保護(hù)作用的機(jī)制之前并不清楚?？茖W(xué)家之前假設(shè)產(chǎn)生相關(guān)蛋白的基因應(yīng)該存在于造成肺結(jié)核的結(jié)合桿菌的基因組中,。Wisconsin大學(xué)的Adel Talaat發(fā)現(xiàn)CsoR是感染小鼠肺結(jié)核的細(xì)菌基因組的一部分。對(duì)DNA的分析使科學(xué)家假設(shè)編譯的相關(guān)蛋白能作為“銅離子泵”將這些離子泵出細(xì)胞,，CsoR是這一過(guò)程中的關(guān)鍵,。
??利用SSRL的加速器，科學(xué)家使用了X射線吸收光譜技術(shù)（XAS）分析純蛋白樣品,。X射線穿過(guò)樣品,，激發(fā)其中銅原子的電子，就能反映樣品的化學(xué)特性,。Giedroc小組能揭示這種蛋白起作用的內(nèi)部機(jī)制,。小組的另一名學(xué)者James Sacchettini還用X射線結(jié)晶學(xué)技術(shù)分析了整個(gè)蛋白質(zhì)的結(jié)構(gòu)。
英文原文：
SSRL Research Helps Uncover the Secrets of an Age-Old Killer
Scientists working in part at the Stanford Synchrotron Radiation Laboratory (SSRL) have discovered a gene for a protein that regulates the cellular response to copper in the bacterium that causes tuberculosis. Copper is a biologically essential element, but its levels within a cell must be carefully controlled because too much can cause cell death. These findings, reported in the January issue of Nature Chemical Biology, explain how a wide variety of bacteria control copper concentrations within their cells, and this understanding could lead to new treatments for tuberculosis.
The research team, led by David Giedroc of Texas A&M University, discovered the gene that encodes a "Copper-sensitive operon Repressor" (CsoR), which controls the production of copper-binding proteins and is present in many types of bacteria.
"Metal ions like copper are the 'Achilles heel' of tuberculosis bacilli and other pathogenic organisms," said Giedroc. "Too much of these ions inside a cell is deadly, but the cell needs them to break down reactive compounds that would otherwise destroy important proteins, DNA, and lipids within the cell."
Copper ions are prevented from damaging the cell by regulatory proteins that sense the metal and turn on the production of other proteins that help mitigate the deadly effects of copper. However, the gene responsible for turning on these proteins and the mechanism behind how the protein works had not been previously identified in many bacteria.
The researchers hypothesized that the gene that encodes the copper-binding protein must appear somewhere in the genome of Mycobacterium tuberculosis, the pathogen responsible for tuberculosis infections in humans. The University of Wisconsin's Adel Talaat, a co-author on the study, had previously shown that CsoR was part of a cluster of genes active in M. tuberculosis infecting the lungs of mice. Analysis of the DNA sequence of another nearby gene led the researchers to hypothesize that it encoded a protein that acts as a "copper pump" that drives excess copper out of the cell, and that CsoR was the critical regulator of this process.
Using the synchrotron facilities at SSRL and the Canadian Light Source (CLS), the researchers used a technique called x-ray absorption spectroscopy (XAS) on purified samples of the copper-binding protein from Mycobacterium tuberculosis. With the XAS technique, a beam of x-rays is passed through a sample, exciting the electrons in the sample's copper atoms, thereby revealing important clues about sample's chemistry and how its atoms are bonded. Using this and other techniques, Giedroc and his team uncovered the chemical mechanism behind the copper-binding protein in M. tuberculosis and thus how the protein functions.
"It's a fundamental new discovery which might, down the road, lead to new treatments for tuberculosis," said University of Saskatchewan's Graham George, who collaborated with Giedroc's team on the experiment. "The x-ray absorption spectroscopy part of the work was vital to understanding how the CsoR protein binds copper."
Another member of Giedroc's team, James Sacchettini of Texas A&M, employed a commonly used technique called x-ray crystallography to help determine the overall structure of the copper-binding protein. With this technique, protein molecules are grown into crystals and then exposed to a beam of x-rays. By measuring the pattern of x-rays scattered by the sample, researchers can map out the arrangement of the atoms in a molecule and gather clues about its function.
