我们体内细胞众多的基因中，只有那些表达的基因使我们成为现在这个样子。特定的蛋白通过结合DNA上的关键位点——包含遗传信息的核酸，调节基因表达。
这些蛋白是怎样识别特定结合位点的？蛋白结构和DNA结构的改变，有时是结合位点内的DNA纽结或急剧弯曲，使得DNA－蛋白紧密结合。
研究人员认为DNA在这种遗传相互作用中是被动的一方。但是由伊利诺斯州大学生物物理学副教授Anjum Ansari发现，DNA并不是所想象的完全被动的。
为了对蛋白－DNA结合时发生的结构变化进行实时检测，Ansari及其同事利用一种细菌来源的检测蛋白，和持续一百亿分之一秒的激光脉冲加热、搅乱蛋白－DNA复合物，观察结合蛋白的动力学改变情况。这是首次利用激光脉冲升温光源法（laser temperature-jump technique，生物通编者译）研究蛋白－DNA复合物动力学。
Ansari说：“止流（stopped-flow）技术可以捕获毫秒时间内出现的生物分子的动力学变化，此次研究的目的是将时长范围缩小到微秒级别以下。”这种技术与止流测量方法结合，可直接观测DNA与蛋白结合过程。
Ansari发现DNA的结合时间级别与先前报道的一个碱基对瞬时降解的时间级别相似。推测，DNA可以自行的弯曲或者打结，蛋白识别弯曲的DNA结构并与之紧密结合。
Ansari及其同事的结论稍微背离传统教条，传统观点认为是蛋白结合DNA，而Ansari等认为DNA“弯曲特性”（bendability）指导蛋白到特定的DNA位点。
Ansari说这个新发现有助于研究蛋白识别特异结合位点的机制，为研发蛋白结合DNA特异位点的药物和以基因为基础的治疗方法提供一臂之力。
英文原文：
Gene-Bender Proteins May Sway to DNA
Among the many genes packed into each cell of our body, those that get turned on, or expressed, are the ones that make us who we are. Certain proteins do the job of regulating gene expression by clasping onto key spots of DNA -- the nucleic acid that contains the genetic instructions.
How does the protein recognize a particular binding site? Structural changes in both the protein and DNA, sometimes with the DNA within the complex kinked or sharply bent, allow for the specific contacts needed for a tight DNA-protein fit.
Scientists think DNA is largely passive in this genetic tango. But new findings by Anjum Ansari, associate professor of biophysics at the University of Illinois at Chicago, suggest DNA may not be the wallflower that many had assumed.
To follow in real time the structural changes that accompany protein-DNA binding, Ansari and her UIC colleagues used a test protein from bacteria and applied a laser pulse lasting about 10 billionths of a second to heat up and disturb the protein-DNA complex. They watched the dynamics of the bound DNA in response to this perturbation.
Ansari's group was the first to apply the laser temperature-jump technique to study the dynamics of a protein-DNA complex.
The studies were done in collaboration with Donald Crothers, Sterling Professor Emeritus of chemistry at Yale University, who examined the protein-DNA interaction with the more traditional stopped-flow technique.
"While stopped-flow technique can capture dynamics of biomolecules occurring on millisecond time-scales or longer, the goal of this study was to extend the time-resolution down to sub-microseconds. It gave us a new time window on probing protein-DNA interactions," Ansari said.
That broader time window, obtained in combination with the stopped-flow measurements, provided the first direct observation of DNA bending when bound to a DNA-bending protein.
"We found that the time-scales on which DNA was bending were very similar to previously reported time-scales on which individual base-pairs that hold the two DNA strands together were transiently breaking. That led us to conclude that the DNA is able to bend or kink on its own, at weak points created by the transient opening of base-pairs, and that the protein recognizes and binds tightly to the bent DNA conformation."
Conclusions by Ansari and her colleagues deviate slightly from the conventional dogma that it is the protein that bends the DNA. She said the results raise important questions about the role that the DNA "bendability" plays in guiding the correct bending protein to the appropriate site on the DNA.
Ansari said the research adds to the basic understanding of how proteins recognize a specific binding site.
"Gaining better insights into protein-DNA interactions that control all aspects of gene regulation may prove useful for rational design of drugs to target specific sites on the DNA, whereby one can ultimately develop better gene-based therapies," she said.
The findings appear in the Dec. 5 issue of the Proceedings of the National Academy of Sciences. Serguei Kuznetsov, research assistant professor of physics at UIC, is first author on the paper; Ansari and Crothers are corresponding authors. Other co-authors include graduate students Paula Vivas, working with Ansari at UIC, and Sawako Sugimura, working with Crothers at Yale.
The research was supported by grants from the National Science Foundation, the American Chemical Society Petroleum Research Fund and the National Institutes of Health.
